Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor?
Open accessAbstract
Most patients with non‐small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations, such as deletions in exon 19 or the L858R mutation in exon 21, respond dramatically to EGFR tyrosine kinase inhibitors (EGFR‐TKI), and their sensitivities to various EGFR‐TKI have been well characterized. Our previous article showed the in vitro sensitivities of EGFR exon 18 mutations to EGFR‐TKI, but little information regarding the sensitivities of other uncommon EGFR mutations is available. First, stable transfectant Ba/F3 cell lines harboring EGFR L858R (Ba/F3‐L858R), L861Q (Ba/F3‐L861Q) or S768I (Ba/F3‐S768I) mutations were created and their drug sensitivities to various EGFR‐TKI were examined. Both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3‐L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3‐L858R cell line. The Ba/F3‐L861Q cell line was similarly sensitive and the Ba/F3‐S768I cell line was less sensitive to osimertinib, compared with the Ba/F3‐L858R cell line. The results of western blot analyses were consistent with these sensitivities. Next, similar experiments were also performed using the KYSE270 (L861Q) and KYSE 450 (S768I) cell lines, and their results were compatible with those of the transfectant Ba/F3 cell lines. Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib. Overall, afatinib might be the optimal EGFR‐TKI against these uncommon EGFR mutations.
AI snapshot
Written from the paper’s full text.
TL;DR
In vitro testing of uncommon EGFR mutations L861Q and S768I showed that both were less sensitive to erlotinib than L858R, while afatinib retained similar potency across all three mutants. The authors conclude that afatinib may be the optimal EGFR-TKI for NSCLC harboring L861Q or S768I, with osimertinib also active against L861Q but less so against S768I.
Key findings
- In Ba/F3 transfectants, IC50 values for erlotinib were 4.5 nM (L858R), 92 nM (L861Q), and 146 nM (S768I); for afatinib, 0.2, 0.5, and 0.7 nM; and for osimertinib, 2.5, 9, and 49 nM, respectively.
- Relative to Ba/F3-L858R, erlotinib IC50 ratios were 20-fold for L861Q and 32-fold for S768I; afatinib ratios were 2.5-fold and 3.5-fold; osimertinib ratios were 3.6-fold for L861Q and 20-fold for S768I.
- Western blot results were consistent with growth inhibition: afatinib inhibited EGFR phosphorylation similarly across mutants, erlotinib inhibited phosphorylation less in L861Q/S768I, and osimertinib inhibited L861Q similarly but S768I less than L858R.
- In KYSE270 (L861Q) and KYSE450 (S768I) cell lines, both were most sensitive to afatinib and least sensitive to erlotinib; osimertinib was as effective as afatinib in KYSE270 but much less effective in KYSE450. IC50 values in KYSE270 were 0.7 μM erlotinib, 0.004 μM afatinib, and 0.03 μM osimertinib; in KYSE450, 1.1 μM, 0.004 μM, and 0.4 μM, respectively.
Methods
- Stable Ba/F3 cell lines expressing EGFR L858R, L861Q, or S768I were created by retroviral transfection; KYSE270 (L861Q) and KYSE450 (S768I) esophageal cancer cell lines were also used.
- Cells were treated with erlotinib, afatinib, or osimertinib; growth inhibition was measured by MTT assay, and EGFR phosphorylation and apoptosis markers were assessed by western blot.
- IC50 values and IC50 ratios relative to Ba/F3-L858R were calculated; experiments were performed in triplicate and analyzed with Student t-test, with P < 0.05 considered significant.
Limitations
- The paper states that binding affinities between tyrosine kinases and EGFR-TKIs and protein structures could not be analyzed; instead, the EGFR crystal structure was based on PDB ID 4G5J.
- The paper states that NSCLC cell lines harboring L861Q or S768I could not be found, so artificially transfected Ba/F3 cells and esophageal cancer cell lines were used instead.
- The paper states that clinical data or samples could not be analyzed because the patient population is too small; evident from the text, the study is entirely in vitro and does not provide direct patient outcomes.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 50 cited sources checked · 0 supported · 0 flagged
- Findingown data
Ba/F3-S768I cell line was less sensitive to osimertinib than the Ba/F3-L858R cell line.
“The Ba/F3‐L861Q cell line was similarly sensitive and the Ba/F3‐S768I cell line was less sensitive to osimertinib, compared with the Ba/F3‐L858R cell line.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
“The Ba/F3‐L861Q cell line was similarly sensitive and the Ba/F3‐S768I cell line was less sensitive to osimertinib, compared with the Ba/F3‐L858R.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
“the IC50 value of osimertinib in the Ba/F3‐S768I cell line was much higher than that in the Ba/F3‐L858R cell line (IC50 ratio, 20‐fold)”
Quote in the paperSubstantial claim - Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
- Findingown data
Ba/F3-L861Q cell line was similarly sensitive to osimertinib as the Ba/F3-L858R cell line.
“The Ba/F3‐L861Q cell line was similarly sensitive and the Ba/F3‐S768I cell line was less sensitive to osimertinib, compared with the Ba/F3‐L858R cell line.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
“The Ba/F3‐L861Q cell line was similarly sensitive and the Ba/F3‐S768I cell line was less sensitive to osimertinib, compared with the Ba/F3‐L858R.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
“The IC50 value of osimertinib in the Ba/F3‐L861Q cell line was not relatively high, compared with that of the Ba/F3‐L858R cell line (IC50 ratio, 3.6‐fold)”
Quote in the paperSubstantial claim - Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
- Findingown data
Phosphorylation level of EGFR was elevated in Ba/F3-L861Q and Ba/F3-S768I cell lines similar to that in the Ba/F3-L858R cell line.
“The phosphorylation level of EGFR was also elevated in the Ba/F3‐L861Q and Ba/F3‐S768I cell lines, similar to that in the Ba/F3‐L858R cell line.”
Quote in the paperSubstantial claim - Findingown data
Ba/F3-L861Q and Ba/F3-S768I cell lines were similarly sensitive to afatinib as the Ba/F3-L858R cell line.
“Both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3‐L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3‐L858R cell line.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
“In contrast, their sensitivities to afatinib were similar to that of the Ba/F3‐L858R cell line.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
“The IC50 ratios of afatinib in the Ba/F3‐L861Q and Ba/F3‐S768I cell lines relative to the Ba/F3‐L858R cell line were less than 5‐fold (2.5‐fold and 3.5‐fold, respectively) (Fig. 2b).”
Quote in the paperSubstantial claim - Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
- Findingown data
Results from KYSE270 and KYSE450 cell lines were compatible with those from the Ba/F3 transfectant cell lines.
“Next, similar experiments were also performed using the KYSE270 (L861Q) and KYSE 450 (S768I) cell lines, and their results were compatible with those of the transfectant Ba/F3 cell lines.”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · hedged
“KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines”
Quote in the paperSubstantial claim- Rests on an assumption: KYSE270 and KYSE450 esophageal cancer cell lines with EGFR L861Q/S768I mutations are valid models for NSCLC harboring the same mutations.
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · hedged
- Findingown data
Western blot results were consistent with the sensitivities observed in growth inhibition assays.
“The results of western blot analyses were consistent with these sensitivities.”
Quote in the paperNot a substantial claim - Findingown data
Both Ba/F3-L861Q and Ba/F3-S768I cell lines were less sensitive to erlotinib compared with the Ba/F3-L858R cell line.
“Both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3‐L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3‐L858R cell line.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
“The Ba/F3‐L861Q and Ba/F3‐S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3‐L858R cell line.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
“The IC50 values of erlotinib in both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines were much greater than that of the Ba/F3‐L858R cell line (IC50 ratio, 20‐fold and 32‐fold, respectively).”
Quote in the paperSubstantial claim - Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · plain
- Findingown data
Osimertinib intermediately inhibited EGFR phosphorylation in the KYSE270 and KYSE450 cell lines.
“Osimertinib intermediately inhibited the phosphorylation.”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“Osimertinib intermediately inhibited the phosphorylation.”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
Phosphorylation of EGFR strongly persisted in the Ba/F3-S768I cell line in the presence of 100 nM osimertinib.
“The phosphorylation of EGFR also strongly persisted in the Ba/F3‐S768I cell line in the presence of 100 nM of osimertinib”
Quote in the paperSubstantial claim - Findingown data
Erlotinib inhibited phosphorylation of EGFR to a lesser degree in Ba/F3-L861Q and Ba/F3-S768I cell lines than in the Ba/F3-L858R cell line.
“erlotinib inhibited the phosphorylation of EGFR to a lesser degree in both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines than in the Ba/F3‐L858R cell line”
- Also stated in: § Differences in epidermal growth factor receptor inhibitory effects of various epidermal growth factor receptor‐tyrosine kinase inhibitors among EGFR L858R, L861Q, and S768I mutations · plain
“erlotinib inhibited the phosphorylation of EGFR to a lesser degree in both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines, compared with the Ba/F3‐L858R cell line.”
Quote in the paperSubstantial claim - Also stated in: § Differences in epidermal growth factor receptor inhibitory effects of various epidermal growth factor receptor‐tyrosine kinase inhibitors among EGFR L858R, L861Q, and S768I mutations · plain
- Findingown data
In the authors' studies, 3G EGFR-TKIs seemed less effective against uncommon EGFR mutations.
“Nevertheless, in our studies, 3G EGFR‐TKI seemed to be less effective against the uncommon EGFR mutations.”
Quote in the paperSubstantial claim - Findingown data
Osimertinib was as effective against the KYSE270 cell line as afatinib.
“Among them, osimertinib was as effective against the KYSE270 cell line as afatinib”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“Osimertinib was as effective for the KYSE270 cell line as afatinib”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
Osimertinib inhibited phosphorylation of EGFR to almost the same degree in the Ba/F3-L861Q cell line as in the Ba/F3-L858R cell line.
“Osimertinib inhibited the phosphorylation of EGFR to almost the same degree in the Ba/F3‐L861Q cell line”
- Also stated in: § Differences in epidermal growth factor receptor inhibitory effects of various epidermal growth factor receptor‐tyrosine kinase inhibitors among EGFR L858R, L861Q, and S768I mutations · plain
“Osimertinib inhibited the phosphorylation of EGFR to almost the same degree in the Ba/F3‐L861Q cell line”
Quote in the paperSubstantial claim - Also stated in: § Differences in epidermal growth factor receptor inhibitory effects of various epidermal growth factor receptor‐tyrosine kinase inhibitors among EGFR L858R, L861Q, and S768I mutations · plain
- Findingown data
IC50 values of erlotinib, afatinib and osimertinib in the KYSE270 cell line were 0.7, 0.004 and 0.03 μM, respectively.
“The IC50 values of erlotinib, afatinib and osimertinib in the KYSE 270 cell line were 0.7, 0.004 and 0.03 μM, respectively”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“The IC50 values of erlotinib, afatinib and osimertinib in the KYSE 270 cell line (L861Q) were 0.7, 0.004 and 0.03 μM, respectively”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
No NSCLC cell line harboring uncommon EGFR mutations such as L861Q or S768I could be found.
“No NSCLC cell line harboring uncommon EGFR mutations, such as EGFR L861Q or S768I mutations, could be found.”
Quote in the paperSubstantial claim - Findingown data
Osimertinib inhibited phosphorylation of EGFR to a lesser degree in the Ba/F3-S768I cell line than in the Ba/F3-L858R cell line.
“but to a lesser degree in the Ba/F3‐S768I cell line, compared with that in the Ba/F3‐L858R cell line”
- Also stated in: § Differences in epidermal growth factor receptor inhibitory effects of various epidermal growth factor receptor‐tyrosine kinase inhibitors among EGFR L858R, L861Q, and S768I mutations · plain
“and to a lesser degree in the Ba/F3‐S768I cell line, compared with that in the Ba/F3‐L858R cell line.”
Quote in the paperSubstantial claim - Also stated in: § Differences in epidermal growth factor receptor inhibitory effects of various epidermal growth factor receptor‐tyrosine kinase inhibitors among EGFR L858R, L861Q, and S768I mutations · plain
- Findingown data
Osimertinib was much less effective than afatinib against the KYSE450 cell line.
“but was much less effective than afatinib against the KYSE450 cell line”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“but was much less effective for the KYSE450 cell line than afatinib.”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
In the KYSE450 cell line, osimertinib's EGFR inhibitory effect was much weaker than afatinib's.
“In particular, in the KYSE450 cell line, its EGFR inhibitory effect was much weaker than that of afatinib (Fig. 5a).”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“In the KYSE450 cell line, especially, the EGFR inhibitory effect of osimertinib was much weaker than that of afatinib.”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
IC50 values of erlotinib, afatinib and osimertinib in the KYSE450 cell line were 1.1, 0.004 and 0.4 μM, respectively.
“and those of erlotinib, afatinib and osimertinib in the KYSE 450 cell line were 1.1, 0.004 and 0.4 μM, respectively”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“while those of erlotinib, afatinib and osimertinib in the KYSE 450 cell line (S768I) were 1.1, 0.004 and 0.4 μM, respectively.”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
In both KYSE270 (L861Q) and KYSE450 (S768I) cell lines, afatinib markedly inhibited EGFR phosphorylation compared with erlotinib.
“In both cell lines, afatinib markedly inhibited the phosphorylation of EGFR, compared with erlotinib (Fig. 5a).”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“In both the KYSE270 (L861Q) and the KYSE450 (S768I) cell lines, afatinib markedly inhibited the phosphorylation of EGFR, compared with erlotinib.”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
Both KYSE270 and KYSE450 cell lines were intermediately sensitive to osimertinib.
“Both cell lines were intermediately sensitive to osimertinib.”
Quote in the paperSubstantial claim - Findingown data
In the KYSE270 cell line, afatinib and osimertinib elevated cleaved caspase-3 expression.
“In the KYSE270 cell line, afatinib and osimertinib elevated the expression level of cleaved caspase‐3”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“In the KYSE270 cell line (L861Q), afatinib and osimertinib induced an expression of cleaved caspase‐3”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
Afatinib inhibited phosphorylation of EGFR to almost the same degree in all transfectant Ba/F3 cell lines.
“Afatinib inhibited the phosphorylation of EGFR to almost the same degree in all of the transfectant Ba/F3 cell lines”
- Also stated in: § Differences in epidermal growth factor receptor inhibitory effects of various epidermal growth factor receptor‐tyrosine kinase inhibitors among EGFR L858R, L861Q, and S768I mutations · plain
“Afatinib inhibited the phosphorylation of EGFR to almost the same degree in all the transfectant Ba/F3 cell lines”
Quote in the paperSubstantial claim - Also stated in: § Differences in epidermal growth factor receptor inhibitory effects of various epidermal growth factor receptor‐tyrosine kinase inhibitors among EGFR L858R, L861Q, and S768I mutations · plain
- Findingown data
In the KYSE450 cell line, only afatinib elevated cleaved caspase-3 expression.
“whereas only afatinib elevated this level in the KYSE450 cell line (Fig. 5b).”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“whereas only afatinib induced the expression of cleaved caspase‐3, in the KYSE450 cell line (S768I).”
Quote in the paperSubstantial claim - Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
- Findingown data
Phosphorylation of EGFR persisted in Ba/F3-L861Q and Ba/F3-S768I cell lines even in the presence of 100 nM erlotinib.
“In particular, the phosphorylation of EGFR persisted in the Ba/F3‐L861Q and Ba/F3‐S768I cell lines even in the presence of 100 nM of erlotinib”
Quote in the paperSubstantial claim - Findingown data
A similar tendency for EGFR L861Q or S768I mutations was observed in the present study.
“and a similar tendency for EGFR L861Q or S768I mutations was observed in the present study.”
Quote in the paperSubstantial claim - Study design and conductown data
EGFR overexpression was confirmed by western blot in the transfectant Ba/F3 cell lines.
“EGFR overexpression was confirmed by a western blot analysis (Fig. 1b)”
- Also stated in: § EGFR L861Q or S768I mutations have an oncogenic activity similar to that of the EGFR L858R mutation · plain
“EGFR overexpression was confirmed by a western blot analysis.”
Quote in the paperSubstantial claim - Also stated in: § EGFR L861Q or S768I mutations have an oncogenic activity similar to that of the EGFR L858R mutation · plain
- Interpretationown data
NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib.
“Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · hedged
“These results suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib”
- Also stated in: § Discussion · hedged
“In conclusion, based on our present in vitro findings, NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib”
Quote in the paperSubstantial claim- Rests on an assumption: In vitro sensitivities of EGFR-mutant cell lines to EGFR-TKIs predict clinical sensitivity in NSCLC patients.
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · hedged
- Premisecitation
Several studies have shown that 1G EGFR-TKI are less effective in patients with NSCLC harboring uncommon EGFR mutations compared with patients harboring common EGFR mutations.
“Several studies, although very small, have shown that 1G EGFR‐TKI are less effective in patients with NSCLC harboring such uncommon EGFR mutations, compared with patients harboring common EGFR mutations.”
Quote in the paperSubstantial claim0 of 9 sources checked- cites [18] Wu JY, Wu SG, Yang CH et al Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res 2008; 14: 4877– 82. 18676761 source
Not checked in the free run.
- cites [19] Arcila ME, Nafa K, Chaft JE et al EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther 2013; 12: 220– 9. 23371856 PMC3714231 source
Not checked in the free run.
- cites [20] Beau‐Faller M, Prim N, Ruppert AM et al Rare EGFR exon 18 and exon 20 mutations in non‐small‐cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC‐IFCT network. Ann Oncol 2014; 25: 126– 31. 24285021 PMC3868323 source
Not checked in the free run.
- cites [21] Watanabe S, Minegishi Y, Yoshizawa H et al Effectiveness of gefitinib against non‐small‐cell lung cancer with the uncommon EGFR mutations G719X and L861Q. J Thorac Oncol 2014; 9: 189– 94. 24419415 PMC4132025 source
Not checked in the free run.
- cites [22] Otsuka T, Mori M, Yano Y et al Effectiveness of tyrosine kinase inhibitors in Japanese patients with non‐small cell lung cancer harboring minor epidermal growth factor receptor mutations: results from a multicenter retrospective study (HANSHIN Oncology Group 0212). Anticancer Res 2015; 35: 3885– 91. 26124334
Not checked in the free run.
- cites [23] Chiu CH, Yang CT, Shih JY et al Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations. J Thorac Oncol 2015; 10: 793– 9. 25668120 source
Not checked in the free run.
- cites [24] Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non‐small‐cell lung cancer: preclinical data and clinical implications. Lancet Oncol 2012; 13: e23– 31. 21764376 source
Not checked in the free run.
- cites [25] Yasuda H, Park E, Yun CH et al Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5: 216ra177. PMC3954775 24353160 source
Not checked in the free run.
- cites [26] Naidoo J, Sima CS, Rodriguez K et al Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: clinical outcomes and response to erlotinib. Cancer 2015; 121: 3212– 20. 26096453 PMC4807634 source
Not checked in the free run.
- Interpretationown data
NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib.
“and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib.”
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · hedged
“and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib.”
- Also stated in: § Discussion · hedged
“and NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib.”
Quote in the paperSubstantial claim- Rests on an assumption: In vitro sensitivities of EGFR-mutant cell lines to EGFR-TKIs predict clinical sensitivity in NSCLC patients.
- Also stated in: § Different sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors in each transfectant Ba/F3 cell line · hedged
- Premisecitation
Afatinib was reported to be clinically effective for patients with NSCLC harboring uncommon EGFR mutations, including exon 18 mutations, in a recent post-hoc analysis.
“Indeed, afatinib was reported to be clinically effective for patients with NSCLC harboring uncommon EGFR mutations, including exon 18 mutations in a recent post‐hoc analysis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Yang JC, Sequist LV, Geater SL et al Clinical activity of afatinib in patients with advanced non‐small‐cell lung cancer harbouring uncommon EGFR mutations: a combined post‐hoc analysis of LUX‐Lung 2, LUX‐Lung 3, and LUX‐Lung 6. Lancet Oncol 2015; 16: 830– 8. 26051236 source
Not checked in the free run.
- Premisecitation
Previous study showed efficacy of afatinib or neratinib against exon 18 mutations.
“In contrast, our previous study, in which the sensitivities to various EGFR‐TKI for exon 18 mutations were investigated in vitro, showed the efficacy of afatinib or neratinib against exon 18 mutations.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] Kobayashi Y, Togashi Y, Yatabe Y et al EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first‐ or third‐generation TKIs. Clin Cancer Res 2015; 21: 5305– 13. 26206867 source
Not checked in the free run.
- Interpretationreasoning
Afatinib might be the optimal EGFR-TKI against these uncommon EGFR mutations.
“Overall, afatinib might be the optimal EGFR‐TKI against these uncommon EGFR mutations.”
Quote in the paperSubstantial claim- Rests on an assumption: In vitro sensitivities of EGFR-mutant cell lines to EGFR-TKIs predict clinical sensitivity in NSCLC patients.
- Rests on an assumption: Similar in vitro sensitivity to afatinib across EGFR mutations is sufficient to conclude afatinib is the optimal EGFR-TKI for patients.
- Interpretationown data
EGFR L861Q and S768I are activating oncogenic mutations similar to the common mutation EGFR L858R.
“These results indicate that both EGFR L861Q and S768I are activating oncogenic mutations similar to the common mutation EGFR L858R.”
Quote in the paperSubstantial claim - Premisecitation
The authors' previous in vitro study demonstrated efficacy of afatinib or neratinib for exon 18 mutation including G719X.
“Our previous in vitro study has demonstrated the efficacy of afatinib or neratinib for the exon 18 mutation, including G719X.27”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Kobayashi Y, Togashi Y, Yatabe Y et al EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first‐ or third‐generation TKIs. Clin Cancer Res 2015; 21: 5305– 13. 26206867 source
Not checked in the free run.
- Premisecitation
The authors' previous in vitro study showed lower efficacy of 3G EGFR-TKIs including osimertinib for EGFR exon 18 mutations.
“Our previous in vitro study showed a lower efficacy of 3G EGFR‐TKI, including osimertinib, for EGFR exon 18 mutations,27”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Kobayashi Y, Togashi Y, Yatabe Y et al EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first‐ or third‐generation TKIs. Clin Cancer Res 2015; 21: 5305– 13. 26206867 source
Not checked in the free run.
- Premisecitation
A combined post-hoc analysis revealed favorable progression-free survival and treatment response for afatinib in patients with NSCLC harboring uncommon EGFR mutations including G719X, L861Q and S768I (objective response rate 77.1%, disease control rate 84.2%, progression-free survival 10.7 months).
“a combined post‐hoc analysis revealed a favorable progression‐free survival and treatment response for afatinib in patients with NSCLC harboring uncommon EGFR mutations, including G719X, L861Q and S768I mutations (objective response rate, 77.1%; disease control rate, 84.2%; progression free survival, 10.7 months).28”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Yang JC, Sequist LV, Geater SL et al Clinical activity of afatinib in patients with advanced non‐small‐cell lung cancer harbouring uncommon EGFR mutations: a combined post‐hoc analysis of LUX‐Lung 2, LUX‐Lung 3, and LUX‐Lung 6. Lancet Oncol 2015; 16: 830– 8. 26051236 source
Not checked in the free run.
- Premisecitation
Like 1G EGFR-TKIs, afatinib might be less effective for most exon 20 insertions in preclinical and clinical studies.
“In contrast, like 1G EGFR‐TKI, afatinib might be less effective for most exon 20 insertions in preclinical and clinical studies.24, 25, 28, 42, 43”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [24] Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non‐small‐cell lung cancer: preclinical data and clinical implications. Lancet Oncol 2012; 13: e23– 31. 21764376 source
Not checked in the free run.
- cites [25] Yasuda H, Park E, Yun CH et al Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5: 216ra177. PMC3954775 24353160 source
Not checked in the free run.
- cites [28] Yang JC, Sequist LV, Geater SL et al Clinical activity of afatinib in patients with advanced non‐small‐cell lung cancer harbouring uncommon EGFR mutations: a combined post‐hoc analysis of LUX‐Lung 2, LUX‐Lung 3, and LUX‐Lung 6. Lancet Oncol 2015; 16: 830– 8. 26051236 source
Not checked in the free run.
- Interpretationown data
The results from the KYSE cell lines were compatible with those from transfectant Ba/F3 cell lines.
“These results were compatible with those of the transfectant Ba/F3 cell lines.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Considering these findings, afatinib might be optimal for patients with NSCLC harboring EGFR uncommon mutations including exon 18 mutations, L861Q and S768I in clinical settings.
“Considering these findings including our studies, 18, 19, 20, 21, 22, 23, 27, 28, 41 afatinib might be optimal for patients with NSCLC harboring the EGFR uncommon mutations including exon 18 mutations, L861Q and S768I in clinical settings.”
- Also stated in: § Discussion · hedged
“Taken together, these findings suggest that afatinib might be optimal for NSCLC patients harboring the uncommon EGFR mutations including exon 18 mutations, L861Q and S768I in clinical settings.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [18] Wu JY, Wu SG, Yang CH et al Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res 2008; 14: 4877– 82. 18676761 source
Not checked in the free run.
- cites [19] Arcila ME, Nafa K, Chaft JE et al EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther 2013; 12: 220– 9. 23371856 PMC3714231 source
Not checked in the free run.
- cites [20] Beau‐Faller M, Prim N, Ruppert AM et al Rare EGFR exon 18 and exon 20 mutations in non‐small‐cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC‐IFCT network. Ann Oncol 2014; 25: 126– 31. 24285021 PMC3868323 source
Not checked in the free run.
- Also stated in: § Discussion · hedged
- Study design and conductown data
Trends similar to those obtained using transfectant Ba/F3 cell lines were confirmed in the KYSE cell lines, even though they are not NSCLC cell lines.
“trends similar to the results obtained using transfectant Ba/F3 cell lines were confirmed in the KYSE cell lines, even though they are not NSCLC cell lines.”
Quote in the paperSubstantial claim - Premisecitation
The authors' previous study showed that EGFR exon 18 mutations are less sensitive to 1G EGFR-TKIs compared with common mutations.
“Our previous study has shown that EGFR exon 18 mutations are less sensitive to 1G EGFR‐TKI, compared with common mutations,27”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] Kobayashi Y, Togashi Y, Yatabe Y et al EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first‐ or third‐generation TKIs. Clin Cancer Res 2015; 21: 5305– 13. 26206867 source
Not checked in the free run.
- Study design and conductreasoning
The study could not analyze clinical data or samples.
“Third, we could not analyze clinical data or samples.”
Quote in the paperSubstantial claim - Interpretationown data
The difference in sensitivities to various EGFR-TKI is caused by the difference in EGFR inhibitory effects of various EGFR-TKI on each EGFR mutation.
“These results are consistent with those of the growth inhibitory assays, indicating that the difference in sensitivities to various EGFR‐TKI is caused by the difference in the EGFR inhibitory effects of various EGFR‐TKI on each EGFR mutation.”
Quote in the paperSubstantial claim - Premisecitation
Many studies have shown that uncommon EGFR mutations are less sensitive to 1G EGFR-TKIs (objective response rate less than 50%) compared with common EGFR mutations.
“many studies have shown that these uncommon EGFR mutations were less sensitive to 1G EGFR‐TKI (objective response rate, less than 50%), compared with common EGFR mutations.18, 19, 20, 21, 22, 23, 24, 25, 26”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [18] Wu JY, Wu SG, Yang CH et al Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res 2008; 14: 4877– 82. 18676761 source
Not checked in the free run.
- cites [19] Arcila ME, Nafa K, Chaft JE et al EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther 2013; 12: 220– 9. 23371856 PMC3714231 source
Not checked in the free run.
- cites [20] Beau‐Faller M, Prim N, Ruppert AM et al Rare EGFR exon 18 and exon 20 mutations in non‐small‐cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC‐IFCT network. Ann Oncol 2014; 25: 126– 31. 24285021 PMC3868323 source
Not checked in the free run.
- Premiseown data
The authors' previous study indicated that afatinib or neratinib might be effective against NSCLC harboring EGFR exon 18 mutations.
“Our previous study also indicated that afatinib or neratinib might be effective against NSCLC harboring EGFR exon 18 mutations.”
Quote in the paperSubstantial claim - Interpretationown data
In the present study, EGFR L861Q or S768I mutation was considered sensitive to afatinib.
“Furthermore, in our present study, the EGFR L861Q or S768I mutation was considered to be sensitive to afatinib.”
Quote in the paperSubstantial claim - Interpretationcitation
These results were consistent with the favorable outcome of afatinib-treated patients with these uncommon EGFR mutations.
“Thus, these results were consistent with the favorable outcome of afatinib‐treated patients with these uncommon EGFR mutations.28”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Yang JC, Sequist LV, Geater SL et al Clinical activity of afatinib in patients with advanced non‐small‐cell lung cancer harbouring uncommon EGFR mutations: a combined post‐hoc analysis of LUX‐Lung 2, LUX‐Lung 3, and LUX‐Lung 6. Lancet Oncol 2015; 16: 830– 8. 26051236 source
Not checked in the free run.
- Premisecitation
Preclinical studies show lower efficacy of 1G EGFR-TKIs for uncommon EGFR mutations.
“Preclinical studies showing a lower efficacy of 1G EGFR‐TKI for such uncommon mutations supports these clinical data.27, 41, 42, 43”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [27] Kobayashi Y, Togashi Y, Yatabe Y et al EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first‐ or third‐generation TKIs. Clin Cancer Res 2015; 21: 5305– 13. 26206867 source
Not checked in the free run.
- cites [41] Kancha RK, von Bubnoff N, Peschel C et al Functional analysis of epidermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapy. Clin Cancer Res 2009; 15: 460– 7. 19147750 source
Not checked in the free run.
- cites [42] Hirano T, Yasuda H, Tani T et al In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non‐small‐cell lung cancer. Oncotarget 2015; 6: 38789– 803. 26515464 PMC4770737 source
Not checked in the free run.
- Interpretationown data
The difference in EGFR inhibitory effects and induction of apoptosis reflected the different sensitivities to various EGFR-TKIs.
“Based on the results of western blot analyses, the difference in the EGFR inhibitory effects and the induction of apoptosis reflected the different sensitivities to various EGFR‐TKI.”
- Also stated in: § Discussion · plain
“We also found that the different EGFR inhibitory effects of EGFR‐TKI reflected the different sensitivities to various EGFR‐TKI.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- May combine two claims. 11
- Classified as probably not a substantial claim. 14
May combine two claims.
Findingown dataBa/F3 and Ba/F3-EGFP cell lines could not grow in the absence of IL-3, while all Ba/F3 cell lines harboring each EGFR mutation (L858R, L861Q or S768I) were able to grow IL-3 independently.
“Although the Ba/F3 and Ba/F3‐EGFP cell lines could not grow in the absence of IL‐3, all the Ba/F3 cell lines harboring each EGFR mutation (L858R, L861Q or S768I) were able to grow IL‐3 independently (Fig. 1c).”
- Also stated in: § EGFR L861Q or S768I mutations have an oncogenic activity similar to that of the EGFR L858R mutation · plain
“The Ba/F3 and Ba/F3‐EGFP cell lines could not grow in the absence of IL‐3, while all the Ba/F3 cell lines harboring each EGFR mutation could grow IL‐3 independently.”
Quote in the paperSubstantial claim- Also stated in: § EGFR L861Q or S768I mutations have an oncogenic activity similar to that of the EGFR L858R mutation · plain
May combine two claims.
Findingown dataBoth KYSE270 and KYSE450 cell lines were most sensitive to afatinib and least sensitive to erlotinib.
“Both the KYSE270 and KYSE450 cell lines were most sensitive to afatinib and least sensitive to erlotinib”
- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
“Both the KYSE270 (L861Q) and KYSE450 (S768I) cell lines were most sensitive to afatinib and least sensitive to erlotinib.”
Quote in the paperSubstantial claim- Also stated in: § KYSE270 and KYSE450 cell lines exhibit a tendency similar to that of the transfectant Ba/F3 cell lines · plain
May combine two claims.
Findingown dataIn the present study, in vitro differences in sensitivities to various EGFR-TKIs and the efficacy of afatinib for both EGFR L861Q and S768I mutations were revealed for the first time.
“In the present study, the uncommon EGFR mutations L861Q and S768I were focused on, and the in vitro differences in sensitivities to various EGFR‐TKI and the efficacy of afatinib for both EGFR L861Q and S768I mutations were revealed for the first time.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationCodon 768 is located in the alpha-C helix, and both codons 858 and 861 are located in the activation loop.
“Codon 768 is located in the alpha‐C helix, and both codons 858 and 861 are located in the activation loop.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites 4G5J
Not checked in the free run.
May combine two claims.
PremisecitationKYSE270 and KYSE450 cell lines carry EGFR L861Q and S768I mutations respectively, according to the COSMIC database.
“According to the Catalogue of Somatic Mutations in Cancer (COSMIC) database (http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/), these cell lines carry uncommon EGFR mutations (KYSE270, L861Q and KYSE450, S768I, respectively).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites COSMIC database
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationIt remains unclear what EGFR-TKI is optimal for patients with NSCLC harboring EGFR L861Q or S768I mutations.
“Although this study also indicated the efficacy of afatinib in patients with NSCLC harboring EGFR L861Q or S768I mutations, it remains unclear what EGFR‐TKI is optimal for patients with NSCLC harboring these uncommon EGFR mutations.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Yang JC, Sequist LV, Geater SL et al Clinical activity of afatinib in patients with advanced non‐small‐cell lung cancer harbouring uncommon EGFR mutations: a combined post‐hoc analysis of LUX‐Lung 2, LUX‐Lung 3, and LUX‐Lung 6. Lancet Oncol 2015; 16: 830– 8. 26051236 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe Ba/F3 cell line is often used as a model system for assessing the effects of kinase oncogenes and their sensitivities to inhibitors.
“The Ba/F3 cell line is often used as a model system for assessing the effects of kinase oncogenes and their sensitivities to inhibitors.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] Jiang J, Greulich H, Janne PA et al Epidermal growth factor‐independent transformation of Ba/F3 cells with cancer‐derived epidermal growth factor receptor mutants induces gefitinib‐sensitive cell cycle progression. Cancer Res 2005; 65: 8968– 74. 16204070
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe experiment was performed in triplicate.
“The experiment was performed in triplicate.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown dataAll mutations in the constructed cell lines were confirmed by sequencing.
“All the mutations were confirmed by sequencing.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationThe Ba/F3 cell line is dependent on IL-3 but is rendered IL-3 independent by activating mutations of tyrosine kinase oncogenes.
“The Ba/F3 cell line is well known to be dependent on IL‐3 but to be rendered IL‐3 independent by induction with activating mutations of tyrosine kinase oncogenes.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] Jiang J, Greulich H, Janne PA et al Epidermal growth factor‐independent transformation of Ba/F3 cells with cancer‐derived epidermal growth factor receptor mutants induces gefitinib‐sensitive cell cycle progression. Cancer Res 2005; 65: 8968– 74. 16204070
Not checked in the free run.
May combine two claims.
Interpretationown dataThe present in vitro study indicated that osimertinib might be effective against EGFR L861Q mutation, but is likely to be less effective against EGFR S768I mutation.
“and the present in vitro study indicated that osimertinib might be effective against the EGFR L861Q mutation, but is likely to be less effective against the EGFR S768I mutation.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationMost studies examining uncommon EGFR mutations are small retrospective studies or case reports, and clinical data are limited because this population is uncommon.
“Most studies examining uncommon EGFR mutations are small retrospective studies or case reports, and clinical data is limited because this population is “uncommon” (G719X, 5%; S768I, 1%; L861Q, 3%; exon 20 insertions, 3%).17”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Roengvoraphoj M, Tsongalis GJ, Dragnev KH et al Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non‐small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation‐positive patients. Cancer Treat Rev 2013; 39: 839– 50. 23768755
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSeveral articles have reported patients with NSCLC harboring uncommon mutation who responded to 1G EGFR-TKI, gefitinib or erlotinib.
“Although several articles have reported patients with NSCLC harboring uncommon mutation who responded to 1G EGFR‐TKI, getitinib or erlotinib,39, 40”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [39] Hellmann MD, Reva B, Yu H et al Clinical and in vivo evidence that EGFR S768I mutant lung adenocarcinomas are sensitive to erlotinib. J Thorac Oncol 2014; 9: e73– 4. 25521405 PMC4655969
Not checked in the free run.
- cites [40] Klughammer B, Brugger W, Cappuzzo F et al Examining treatment outcomes with erlotinib in patients with advanced non‐small cell lung cancer whose tumors harbor uncommon EGFR nutations. J Thorac Oncol 2016; 11: 545– 55. 26773740 source
Not checked in the free run.
May combine two claims.
PremisecitationBoth 2G and 3G EGFR-TKIs are irreversible small-molecule inhibitors that covalently bind to EGFR kinase by targeting cysteine-797 in the ATP binding pocket, and 3G EGFR-TKIs are considered more specific for EGFR sensitizing mutations than 2G EGFR-TKIs.
“Both 2G and 3G EGFR‐TKI are irreversible small‐molecule inhibitors that covalently bind to EGFR kinase by targeting the cysteine‐797 residue, located in the ATP binding pocket, and 3G EGFR‐TKI are considered to be more specific for EGFR sensitizing mutations than 2G EGFR‐TKI.12, 13, 14”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [12] Zhou W, Ercan D, Chen L et al Novel mutant‐selective EGFR kinase inhibitors against EGFR T790M. Nature 2009; 462: 1070– 4. 20033049 PMC2879581 source
Not checked in the free run.
- cites [13] Walter AO, Sjin RT, Haringsma HJ et al Discovery of a mutant‐selective covalent inhibitor of EGFR that overcomes T790M‐mediated resistance in NSCLC. Cancer Discov 2013; 3: 1404– 15. 24065731 PMC4048995 source
Not checked in the free run.
- cites [14] Cross DA, Ashton SE, Ghiorghiu S et al AZD9291, an irreversible EGFR TKI, overcomes T790M‐mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 2014; 4: 1046– 61. 24893891 PMC4315625 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe present findings are consistent with previous clinical and in vitro studies.
“These findings are consistent with previous clinical and in vitro studies.18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 37, 38, 39”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [18] Wu JY, Wu SG, Yang CH et al Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res 2008; 14: 4877– 82. 18676761
Not checked in the free run.
- cites [19] Arcila ME, Nafa K, Chaft JE et al EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther 2013; 12: 220– 9. 23371856 PMC3714231
Not checked in the free run.
- cites [20] Beau‐Faller M, Prim N, Ruppert AM et al Rare EGFR exon 18 and exon 20 mutations in non‐small‐cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC‐IFCT network. Ann Oncol 2014; 25: 126– 31. 24285021 PMC3868323 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationSeveral studies indicate that different EGFR inhibitory effects of EGFR-TKIs might be associated with different structural-based interactions.
“Several studies, in which affinities between kinases and various EGFR‐TKI were investigated, indicate that the different EGFR inhibitory effects of EGFR‐TKI might be associated with the different structural‐based interactions.25, 44”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [25] Yasuda H, Park E, Yun CH et al Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med 2013; 5: 216ra177. PMC3954775 24353160 source
Not checked in the free run.
- cites [44] Davis MI, Hunt JP, Herrgard S et al Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol 2011; 29: 1046– 51. 22037378 source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningThe in vitro study may help clinicians select an appropriate EGFR-TKI in such subsets of NSCLC patients.
“Our in vitro study may help clinicians to select an appropriate EGFR‐TKI in such subsets of NSCLC patients.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationUncommon EGFR mutations account for only 10% of all EGFR mutations in NSCLC.
“although uncommon EGFR mutations account for only 10% of all EGFR mutations in NSCLC.17”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Roengvoraphoj M, Tsongalis GJ, Dragnev KH et al Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non‐small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation‐positive patients. Cancer Treat Rev 2013; 39: 839– 50. 23768755
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe Ba/F3 cell line has often been used in many studies investigating EGFR mutations.
“the Ba/F3 cell line has often been used in many studies investigating EGFR mutations,24, 27, 36, 41, 42”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [24] Yasuda H, Kobayashi S, Costa DB. EGFR exon 20 insertion mutations in non‐small‐cell lung cancer: preclinical data and clinical implications. Lancet Oncol 2012; 13: e23– 31. 21764376 source
Not checked in the free run.
- cites [27] Kobayashi Y, Togashi Y, Yatabe Y et al EGFR exon 18 mutations in lung cancer: molecular predictors of augmented sensitivity to afatinib or neratinib as compared with first‐ or third‐generation TKIs. Clin Cancer Res 2015; 21: 5305– 13. 26206867 source
Not checked in the free run.
- cites [36] Jiang J, Greulich H, Janne PA et al Epidermal growth factor‐independent transformation of Ba/F3 cells with cancer‐derived epidermal growth factor receptor mutants induces gefitinib‐sensitive cell cycle progression. Cancer Res 2005; 65: 8968– 74. 16204070
Not checked in the free run.
May combine two claims.
Study design and conductreasoningThe study did not use NSCLC cell lines but used artificially transfected Ba/F3 cell lines and esophageal cancer cell lines, because NSCLC cell lines harboring uncommon EGFR mutations such as L861Q or S768I could not be found.
“Second, we did not use NSCLC cell lines, but rather artificially transfected Ba/F3 cell lines and esophageal cancer cell lines, because we could not find NSCLC cell lines harboring uncommon EGFR mutations such as the EGFR L861Q or S768I mutations.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRecent preclinical studies revealed that osimertinib might be partially effective for exon 20 insertions.
“Recent preclinical studies revealed that osimertinib might be partially effective for exon 20 insertions.42, 43”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [42] Hirano T, Yasuda H, Tani T et al In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non‐small‐cell lung cancer. Oncotarget 2015; 6: 38789– 803. 26515464 PMC4770737 source
Not checked in the free run.
- cites [43] Yang M, Xu X, Cai J et al NSCLC harboring EGFR exon‐20 insertions after the regulatory C‐helix of kinase domain responds poorly to known EGFR inhibitors. Int J Cancer 2016; 139: 171– 6. 26891175
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe study could not analyze binding affinities between tyrosine kinases and EGFR-TKIs or protein structures; instead, the crystal structure of EGFR was determined using the PDB database.
“First, neither the binding affinities between tyrosine kinases and EGFR‐TKI nor the protein structures could be analyzed. Instead, we determined the crystal structure of EGFR using the PDB database.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
In vitro sensitivities of EGFR-mutant cell lines to EGFR-TKIs predict clinical sensitivity in NSCLC patients.
“Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib”
“Overall, afatinib might be the optimal EGFR‐TKI against these uncommon EGFR mutations.”
The paper relies on this without support.
Little information regarding the sensitivities of other uncommon EGFR mutations is available.
“little information regarding the sensitivities of other uncommon EGFR mutations is available.”
“while less information about the sensitivities of uncommon EGFR mutations is available.”
The paper relies on this without support.
KYSE270 and KYSE450 esophageal cancer cell lines with EGFR L861Q/S768I mutations are valid models for NSCLC harboring the same mutations.
“No NSCLC cell line harboring uncommon EGFR mutations, such as EGFR L861Q or S768I mutations, could be found. Instead, the eshopageal cancer cell lines KYSE270 (L861Q) and KYSE450 (S768I) were used to evaluate the sensitivities to various EGFR‐TKI, the EGFR signal and apoptosis.”
The paper relies on this without support.
Similar in vitro sensitivity to afatinib across EGFR mutations is sufficient to conclude afatinib is the optimal EGFR-TKI for patients.
“Overall, afatinib might be the optimal EGFR‐TKI against these uncommon EGFR mutations.”
The paper relies on this without support.
Few reports regarding the effectiveness of 3G EGFR-TKIs against patients with NSCLC harboring uncommon EGFR mutations are available.
“Few reports regarding the effectiveness of 3G EGFR‐TKI against patients with NSCLC harboring uncommon EGFR mutations are available.”
The paper relies on this without support.
The number of patients with NSCLC harboring such uncommon mutations is too small to show clinical data.
“The number of patients with NSCLC harboring such uncommon mutations is too small to show such data.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
L861Q is less sensitive to erlotinib (IC50 92-103 nM) or gefitinib (IC50 170 nM) compared with L858R (IC50 4.5-6 nM), but shows more similar sensitivity to afatinib and osimertinib (IC50 0.5 and 9 nM, respectively) than L858R (IC50 0.2 and 2.5 nM, respectively).
“Preclinical data suggest that this mutation is sensitive to various EGFR TKI, although it is less sensitive to erlotinib (IC50 92–103 nM) or gefitinib (IC50 170 nM), compared with L858R (IC50 4.5–6 nM), but shows more similar sensitivity to afatinib and osimertinib (IC50 0.5 and 9 nM, respectively) than L858R (IC50 0.2 and 2.5 nM, respectively) [34,85].”
L861Q is the second most frequent exon 21 mutation after L858R, accounts for approximately 1-2% of all EGFR mutations, and has oncogenic activity similar to L858R.
“The second most frequent exon 21 mutation after L858R is the point mutation L861Q that accounts for approximately 1–2% of all EGFR mutations [42,84] and has oncogenic activity similar to the L858R mutation [85].”
S768I mutations exhibit higher sensitivity to afatinib in preclinical models compared with first-/third-generation EGFR TKIs, with an ORR of 100% and a median PFS of 14.7 months in the combined analysis of the LUX-Lung 2, 3, and 6 trials.
“Similarly, S768I mutations exhibit differential sensitivity to EGFR TKIs, with a higher sensitivity to afatinib in preclinical models compared with first-/third-generation EGFR TKIs [85], with an ORR of 100% and a median PFS of 14.7 months in the combined analysis of the LUX-Lung 2, 3, and 6 trials [37].”
In preclinical studies, the L861Q mutation is resistant to first-generation TKIs, whereas it might be sensitive to afatinib or osimertinib.
“In preclinical studies, the L861Q mutation is resistant to fi rst-generation TKIs, whereas it might be sensitive to afatinib or osimertinib. 28-31”
From Osimertinib for Patients With Non–Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09) (2020) · cites this paper as [30]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
KYSE270 osimertinib is described as equally effective as afatinib
MinorThe reported IC50 for osimertinib in KYSE270 cells is 0.03 μM, 7.5 times the 0.004 μM reported for afatinib. The stated equal effectiveness is inconsistent with those values.
“osimertinib was as effective against the KYSE270 cell line as afatinib”
“The IC50 values of erlotinib, afatinib and osimertinib in the KYSE 270 cell line were 0.7, 0.004 and 0.03 μM, respectively”
Cites
Rosell, R., Carcereny, E., Gervais, R., Vergnenegre, A., Massuti, B., Felip, E., Palmero, R., Garcia-Gomez, R., Pallares, C., Sanchez, J. M., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70393-x · Cited by 5,489 · see citing works
Mitsudomi, T., Morita, S., Yatabe, Y., Negoro, S., Okamoto, I., Tsurutani, J., Seto, T., Satouchi, M., Tada, H., Hirashima, T., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70364-x · Cited by 4,090 · see citing works
Self-citationZhou, C., Wu, Y.-L., Chen, G., Feng, J., Liu, X.-Q., Wang, C., Zhang, S., Wang, J., Zhou, S., Ren, S., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70184-x · Cited by 4,081 · see citing works
Sequist, L. V., Yang, J. C.-H., Yamamoto, N., O'Byrne, K., Hirsh, V., Mok, T., Geater, S. L., Orlov, S., Tsai, C.-M., Boyer, M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.2806 · Cited by 3,228 · see citing works
Cancer treatment and survivorship statistics, 2014
Desantis, C. E., Lin, C. C., Mariotto, A. B., Siegel, R. L., Stein, K., Kramer, J. L., Alteri, R., Robbins, A. S., & Jemal, A. (2014) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21235 · Cited by 2,781 · see citing works
Comprehensive analysis of kinase inhibitor selectivity
Davis, M. I., Hunt, J. P., Herrgard, S., Ciceri, P., Wodicka, L. M., Pallares, G., Hocker, M., Treiber, D. K., & Zarrinkar, P. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1990 · Cited by 2,409 · see citing works
Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer
Rosell, R., Moran, T., Queralt, C., Porta, R., Cardenal, F., Camps, C., Majem, M., Lopez-Vivanco, G., Isla, D., Provencio, M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0904554 · Cited by 2,373 · see citing works
Cross, D. A. E., Ashton, S. E., Ghiorghiu, S., Eberlein, C., Nebhan, C. A., Spitzler, P. J., Orme, J. P., Finlay, M. R. V., Ward, R. A., Mellor, M. J., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0337 · Cited by 2,246 · see citing works
AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer
Jänne, P. A., Yang, J. C.-H., Kim, D.-W., Planchard, D., Ohe, Y., Ramalingam, S. S., Ahn, M.-J., Kim, S.-W., Su, W.-C., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411817 · Cited by 2,116 · see citing works
Wu, Y.-L., Zhou, C., Hu, C.-P., Feng, J., Lu, S., Huang, Y., Li, W., Hou, M., Shi, J. H., Lee, K. Y., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70604-1 · Cited by 1,978 · see citing works
Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs
Kris, M. G., Johnson, B. E., Berry, L. D., Kwiatkowski, D. J., Iafrate, A. J., Wistuba, I. I., Varella-Garcia, M., Franklin, W. A., Aronson, S. L., Su, P.-F., et al. (2014) · JAMA · doi:10.1001/jama.2014.3741 · Cited by 1,724 · see citing works
Fukuoka, M., Wu, Y.-L., Thongprasert, S., Sunpaweravong, P., Leong, S.-S., Sriuranpong, V., Chao, T.-Y., Nakagawa, K., Chu, D.-T., Saijo, N., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.4235 · Cited by 1,581 · see citing works
Novel mutant-selective EGFR kinase inhibitors against EGFR T790M
Zhou, W., Ercan, D., Chen, L., Yun, C.-H., Li, D., Capelletti, M., Cortot, A. B., Chirieac, L., Iacob, R. E., Padera, R., et al. (2009) · Nature · doi:10.1038/nature08622 · Cited by 1,013 · see citing works
Yang, J. C.-H., Sequist, L. V., Geater, S. L., Tsai, C.-M., Mok, T. S. K., Schuler, M., Yamamoto, N., Yu, C.-J., Ou, S.-H. I., Zhou, C., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00026-1 · Cited by 1,002 · see citing works
Solca, F., Dahl, G., Zoephel, A., Bader, G., Sanderson, M., Klein, C., Kraemer, O., Himmelsbach, F., Haaksma, E., & Adolf, G. R. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.197756 · Cited by 865 · see citing works
Midha, A., Dearden, S. P., & McCormack, R. (2015) · Europe PMC (PubMed Central) · Cited by 843 · see citing works
Rociletinib in <i>EGFR</i>-Mutated Non–Small-Cell Lung Cancer
Sequist, L. V., Soria, J.-C., Goldman, J. W., Wakelee, H. A., Gadgeel, S. M., Varga, A., Papadimitrakopoulou, V., Solomon, B. J., Oxnard, G. R., Dziadziuszko, R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1413654 · Cited by 665 · see citing works
Walter, A. O., Sjin, R. T. T., Haringsma, H. J., Ohashi, K., Sun, J., Lee, K., Dubrovskiy, A., Labenski, M., Zhu, Z., Wang, Z., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0314 · Cited by 620 · see citing works
Yasuda, H., Kobayashi, S., & Costa, D. B. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70129-2 · Cited by 610 · see citing works
Mitsudomi, T., & Yatabe, Y. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00607.x · Cited by 606 · see citing works
Self-citationYasuda, H., Park, E., Yun, C.-H., Sng, N. J., Lucena-Araujo, A. R., Yeo, W.-L., Huberman, M. S., Cohen, D. W., Nakayama, S., Ishioka, K., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007205 · Cited by 571 · see citing works
Inoue, A., Kobayashi, K., Maemondo, M., Sugawara, S., Oizumi, S., Isobe, H., Gemma, A., Harada, M., Yoshizawa, H., Kinoshita, I., et al. (2013) · Annals of Oncology · doi:10.1093/annonc/mds214 · Cited by 540 · see citing works
Self-citationCharacterization of 21 newly established esophageal cancer cell lines
Shimada, Y., Imamura, M., Wagata, T., Yamaguchi, N., & Tobe, T. (1992) · Cancer · doi:10.1002/1097-0142(19920115)69:2 · Cited by 494 · see citing works
Arcila, M. E., Nafa, K., Chaft, J. E., Rekhtman, N., Lau, C., Reva, B. A., Zakowski, M. F., Kris, M. G., & Ladanyi, M. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0620 · Cited by 473 · see citing works
Beau-Faller, M., Prim, N., Ruppert, A.-M., Nanni-Metéllus, I., Lacave, R., Lacroix, L., Escande, F., Lizard, S., Pretet, J.-L., Rouquette, I., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdt418 · Cited by 324 · see citing works
Wu, J.-Y., Wu, S.-G., Yang, C.-H., Gow, C.-H., Chang, Y.-L., Yu, C.-J., Shih, J.-Y., & Yang, P.-C. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5123 · Cited by 319 · see citing works
Chiu, C.-H., Yang, C.-T., Shih, J.-Y., Huang, M.-S., Su, W.-C., Lai, R.-S., Wang, C.-C., Hsiao, S.-H., Lin, Y.-C., Ho, C.-L., et al. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000504 · Cited by 241 · see citing works
Naidoo, J., Sima, C. S., Rodriguez, K., Busby, N., Nafa, K., Ladanyi, M., Riely, G. J., Kris, M. G., Arcila, M. E., & Yu, H. A. (2015) · Cancer · doi:10.1002/cncr.29493 · Cited by 211 · see citing works
Watanabe, S., Minegishi, Y., Yoshizawa, H., Maemondo, M., Inoue, A., Sugawara, S., Isobe, H., Harada, M., Ishii, Y., Gemma, A., et al. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000048 · Cited by 204 · see citing works
Kobayashi, Y., Togashi, Y., Yatabe, Y., Mizuuchi, H., Jangchul, P., Kondo, C., Shimoji, M., Sato, K., Suda, K., Tomizawa, K., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1046 · Cited by 203 · see citing works
Self-citationJiang, J., Greulich, H. E., Janne, P. A., Sellers, W. R., Meyerson, M. M., & Griffin, J. D. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1829 · Cited by 188 · see citing works
Yatabe, Y., Kerr, K. M., Utomo, A., Rajadurai, P., Tran, V. K., Du, X., Chou, T.-Y., Enriquez, M. L. D., Lee, G. K., Iqbal, J., et al. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000422 · Cited by 182 · see citing works
Kancha, R. K., von Bubnoff, N., Peschel, C., & Duyster, J. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1757 · Cited by 168 · see citing works
Hirano, T., Yasuda, H., Tani, T., Hamamoto, J., Oashi, A., Ishioka, K., Arai, D., Nukaga, S., Miyawaki, M., Kawada, I., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5887 · Cited by 165 · see citing works
Roengvoraphoj, M., Tsongalis, G. J., Dragnev, K. H., & Rigas, J. R. (2013) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2013.05.001 · Cited by 120 · see citing works
Klughammer, B., Brugger, W., Cappuzzo, F., Ciuleanu, T., Mok, T., Reck, M., Tan, E. H., Delmar, P., Klingelschmitt, G., Yin, A.-Y., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2015.12.107 · Cited by 98 · see citing works
Jachimczak, P., Hessdörfer, B., Fabel, K., Wismeth, C., Brysch, W., Schlingensiepen, K., Bauer, A., Blesch, A., & Bogdahn, U. (1996) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19960126)65:3 · Cited by 82 · see citing works
Yang, M., Xu, X., Cai, J., Ning, J., Wery, J. P., & Li, Q. (2016) · International Journal of Cancer · doi:10.1002/ijc.30047 · Cited by 55 · see citing works
Togashi, Y., Hayashi, H., Terashima, M., Velasco, M. A. D., Sakai, K., Fujita, Y., Tomida, S., Nakagawa, K., & Nishio, K. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000353 · Cited by 53 · see citing works
Self-citationTanaka, H., Shimada, Y., Imamura, M., Shibagaki, I., & Ishizaki, K. (1997) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19970207)70:4 · Cited by 52 · see citing works
Otsuka, T., Mori, M., Yano, Y., Uchida, J., Nishino, K., Kaji, R., Hata, A., Hattori, Y., Urata, Y., Kaneda, T., et al. (2015) · PubMed · Cited by 28 · see citing works
Clinical and in vivo Evidence that EGFR S768I Mutant Lung Adenocarcinomas Are Sensitive to Erlotinib
Hellmann, M. D., Reva, B. A., Yu, H. A., Rusch, V. W., Rizvi, N. A., Kris, M. G., & Arcila, M. E. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000221 · Cited by 26 · see citing works
An activating ALK gene mutation in ALK IHC-positive/FISH-negative nonsmall-cell lung cancer
Togashi, Y., Mizuuchi, H., Kobayashi, Y., Hayashi, H., Terashima, M., Sakai, K., Banno, E., Mizukami, T., Nakamura, Y., Velasco, M. A. D., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv240 · Cited by 15 · see citing works
Self-citationMaegawa, M., Arao, T., Yokote, H., MATSUMOTO, K. Y., Kudo, K., Tanaka, K., Kaneda, H., Fujita, Y., Ito, F., & Nishio, K. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2008.01071.x · Cited by 14 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Jordan, E. J., Kim, H. R., Arcila, M. E., Barron, D., Chakravarty, D., Gao, J., Chang, M. T., Ni, A., Kundra, R., Jonsson, P., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1337 · Cited by 643 · see citing works
Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer
Harrison, P. T., Vyse, S., & Huang, P. H. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.09.015 · Cited by 625 · see citing works
Kobayashi, Y., & Mitsudomi, T. (2016) · Cancer Science · doi:10.1111/cas.12996 · Cited by 413 · see citing works
Self-citationCho, J. H., Lim, S. H., An, H. J., Kim, K. H., Park, K. U., Kang, E. J., Choi, Y. H., Ahn, M. S., Lee, M. H., Sun, J.-M., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.00931 · Cited by 358 · see citing works
Therapeutic advances of targeting receptor tyrosine kinases in cancer
Tomuleasa, C., Tigu, A.-B., Munteanu, R. A., Moldovan, C. S., Kegyes, D., Onaciu, A., Gulei, D., Ghiaur, G., Einsele, H., & Croce, C. M. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01899-w · Cited by 279 · see citing works
Uncommon EGFR mutations in advanced non-small cell lung cancer
O'Kane, G. M., Bradbury, P. A., Feld, R. D., Leighl, N. B., Liu, G., Pisters, K.-M., Kamel‐Reid, S., Tsao, M., & Shepherd, F. A. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.04.016 · Cited by 152 · see citing works
Gristina, V., Malapelle, U., Galvano, A., Pisapia, P., Pepe, F., Rolfo, C. D., Tortorici, S., Bazan, V., Troncone, G., & Russo, A. D. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.101994 · Cited by 123 · see citing works
Russo, A., Franchina, T., Ricciardi, G., Battaglia, A., Picciotto, M., & Adamo, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061431 · Cited by 110 · see citing works
Reita, D., Pabst, L., Pencreach, E., Guérin, É., Dano, L., Rimelen, V., Voegeli, A., Vallat, L. D., Mascaux, C., & Beau‐Faller, M. (2021) · Cancers · doi:10.3390/cancers13194926 · Cited by 106 · see citing works
The next tier of EGFR resistance mutations in lung cancer
Tumbrink, H. L., Heimsoeth, A., & Sos, M. L. (2020) · Oncogene · doi:10.1038/s41388-020-01510-w · Cited by 101 · see citing works
Tyrosine Kinase Receptors in Oncology
Esteban-Villarrubia, J., Castillo, J. J. S., Pozas, J., Román, M. S., Orejana, I., Torres-Jiménez, J., Carrato, A., Alonso‐Gordoa, T., & Molina‐Cerrillo, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228529 · Cited by 100 · see citing works
Shen, Y.-C., Tseng, G.-C., Tu, C.-Y., Chen, W.-C., Liao, W.-C., Chen, W.-C., Li, C.-H., Chen, H.-J., & Hsia, T.-C. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.06.007 · Cited by 99 · see citing works
Cracking the EGFR code: Cancer biology, resistance mechanisms, and future therapeutic frontiers
Du, Y.-F., Karatekin, F., Wang, W. K., Hong, W., & Gandhi, T. K. B. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100076 · Cited by 86 · see citing works
Masood, A., Kancha, R. K., & Subramanian, J. (2019) · Seminars in Oncology · doi:10.1053/j.seminoncol.2019.08.004 · Cited by 83 · see citing works
Khaddour, K., Jonna, S., Deneka, A. Y., Patel, J. D., Abazeed, M. E., Golemis, E. A., Borghaei, H., & Boumber, Y. (2021) · Cancers · doi:10.3390/cancers13133164 · Cited by 65 · see citing works
Masuzawa, K., Yasuda, H., Hamamoto, J., Nukaga, S., Hirano, T., Kawada, I., Naoki, K., Soejima, K., & Betsuyaku, T. (2017) · Oncotarget · doi:10.18632/oncotarget.22297 · Cited by 53 · see citing works
Pilotto, S., Rossi, A., Vavalà, T., Follador, A., Tiseo, M., Galetta, D., Morabito, A., Di Maio, M., Martelli, O., Caffo, O., et al. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2017.05.016 · Cited by 46 · see citing works
Madic, J., Jovelet, C., Lopez, J., André, B., Fatien, J., Miran, I., Honoré, A., Mezquita, L., Besse, B., Lacroix, L., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.26446 · Cited by 46 · see citing works
Wang, S., & Li, J. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s198945 · Cited by 42 · see citing works
Liu, Z., Chen, Z., Wang, J., Zhang, M., Li, Z., Wang, S., Dong, B., Zhang, C., Gao, J., & Shen, L. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0651-z · Cited by 40 · see citing works
Patient-Derived Cells to Guide Targeted Therapy for Advanced Lung Adenocarcinoma
Kim, S., Lee, J. Y., Kim, D., Joo, H. S., Yun, M. R., Jung, D., Yun, J., Heo, S. G., Ahn, B., Park, C. W., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-56356-4 · Cited by 38 · see citing works
Wang, C., Zhao, K., Hu, S., Wei, D., Gong, Y. Q., & Xie, C. (2023) · The Oncologist · doi:10.1093/oncolo/oyad111 · Cited by 29 · see citing works
Wu, S., Yu, C., Yang, J. C., & Shih, J. (2020) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835920946156 · Cited by 27 · see citing works
Villaruz, L., Wang, X., Bertino, E. M., Gu, L., Antonia, S. J., Burns, T. F., Clarke, J. M., Crawford, J., Evans, T. L., Friedland, D., et al. (2023) · ESMO Open · doi:10.1016/j.esmoop.2023.101183 · Cited by 27 · see citing works
Syahruddin, E., Wulandari, L., Muktiati, N. S., Setijadi, A. R., Soeroso, N. N., Ermayanti, S., Levi, M., Hidajat, H., Widjajahakim, G., & Utomo, A. R. H. (2018) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s154116 · Cited by 26 · see citing works
Yang, S., Mao, S., Li, X., Zhao, C., Liu, Q., Yu, X., Wang, Y., Liu, Y., Pan, Y., Wang, C., et al. (2019) · Lung Cancer · doi:10.1016/j.lungcan.2019.11.018 · Cited by 25 · see citing works
Genetic alterations shaping tumor response to anti-EGFR therapies
Vaquero, J., Pavy, A., Gonzalez‐Sanchez, E., Meredith, M., Arbelaiz, A., & Fouassier, L. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100863 · Cited by 24 · see citing works
Morán, T., Taus, Á., Arriola, E., Aguado, C., Dómine, M., Rueda, A. G., Calles, A., Cedrés, S., Viñolas, N., Isla, D., et al. (2020) · Clinical Lung Cancer · doi:10.1016/j.cllc.2020.04.011 · Cited by 23 · see citing works
Tan, J., Hu, C., Deng, P., Wan, R., Cao, L., Li, M., Yang, H., Gu, Q., An, J., & Jiang, J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.646577 · Cited by 22 · see citing works
Clinical significance of Akt2 in advanced pancreatic cancer treated with erlotinib
Banno, E., Togashi, Y., Velasco, M. A. D., Mizukami, T., Nakamura, Y., Terashima, M., Sakai, K., Fujita, Y., Kamata, K., Kitano, M., et al. (2017) · International Journal of Oncology · doi:10.3892/ijo.2017.3961 · Cited by 22 · see citing works
Self-citationNew therapeutic approaches to overcoming resistant EGFR exon 20 alterations
Li, A. M., Boichard, A., Felip, E., & Kurzrock, R. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.102990 · Cited by 19 · see citing works
Singh, V., Nambirajan, A., Malik, P. S., Thulkar, S. P., Pandey, R. M., Luthra, K., Arava, S., Ray, R., Mohan, A., & Jain, D. (2020) · Lung Cancer · doi:10.1016/j.lungcan.2020.07.038 · Cited by 19 · see citing works
Sehgal, K., Rangachari, D., VanderLaan, P. A., Kobayashi, S. S., & Costa, D. B. (2020) · The Oncologist · doi:10.1002/onco.13537 · Cited by 18 · see citing works
Chen, L., Zhou, Y., Gan, C., Wang, X., Liu, Y., Dong, C., He, R., & Yang, J. (2022) · Cancer Investigation · doi:10.1080/07357907.2022.2069254 · Cited by 17 · see citing works
Yu, S., Zhang, Y., Pan, Y., Cheng, C., Sun, Y., & Chen, H. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s131999 · Cited by 16 · see citing works
Agatsuma, N., Yasuda, Y., & Ozasa, H. (2017) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2017.04.028 · Cited by 15 · see citing works
The Development of 3-substituted Indolin-2-one Derivatives as Kinase Inhibitors for Cancer Therapy
Xu, C., Liu, Y., & Zhao, G. (2021) · Current Medicinal Chemistry · doi:10.2174/0929867328666210831142311 · Cited by 15 · see citing works
Watanabe, M., Oizumi, S., Kiuchi, S., Yamada, N., Yokouchi, H., Fukumoto, S., & Harada, M. (2017) · Internal Medicine · doi:10.2169/internalmedicine.9565-17 · Cited by 14 · see citing works
Kimura, S., Tanaka, K., Harada, T., Liu, R., Shibahara, D., Kawano, Y., Nakanishi, Y., & Okamoto, I. (2018) · Cancer Science · doi:10.1111/cas.13787 · Cited by 13 · see citing works
Xu, H., Yang, G., Liu, R., Yang, Y., Li, W., Li, J., Hao, X., Xing, P., & Wang, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.976731 · Cited by 13 · see citing works
Second-Line Treatment of NSCLC—The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms
Köhler, J. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00009 · Cited by 13 · see citing works
Current management of uncommon EGFR mutations in non-small cell lung cancer
Trinh, J. Q., & Abughanimeh, O. K. M. (2024) · Current Problems in Cancer · doi:10.1016/j.currproblcancer.2024.101064 · Cited by 12 · see citing works
EGFR L861Q Mutation in a Metastatic Solid-pseudopapillary Neoplasm of the Pancreas
Neill, K., Saller, J. J., Diffalha, S. A., Centeno, B. A., Malafa, M. P., & Coppola, D. (2018) · Cancer Genomics & Proteomics · doi:10.21873/cgp.20078 · Cited by 12 · see citing works
Lei, L., Wang, W., Zhu, Y., Li, J., Fang, Y., Wang, H., Zhuang, W., Zhang, Y.-B., Wang, L., Fang, M., et al. (2019) · Cancer Medicine · doi:10.1002/cam4.2652 · Cited by 12 · see citing works
Oh, S. Y., Park, S., Lee, S.-Y., Lee, E. J., Kim, T. H., Choi, S., Park, S. Y., Kim, J. H., Lim, S. M., Lee, J. B., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.101929 · Cited by 11 · see citing works
Miura, S., Yamanaka, T., Kato, T., Ikeda, S., Horinouchi, H., Ichihara, E., Kanazu, M., Takiguchi, Y., Tanaka, K., Gotô, Y., et al. (2020) · Clinical Lung Cancer · doi:10.1016/j.cllc.2020.05.011 · Cited by 11 · see citing works
Prevalence of EGFR Mutations in Lung Cancer in Uruguayan Population
Berois, N., Touya, D., Ubillos, L., Bertoni, B., Osinaga, E., & Varangot, M. (2017) · Journal of Cancer Epidemiology · doi:10.1155/2017/6170290 · Cited by 10 · see citing works
Tanizaki, J., Banno, E., Togashi, Y., Hayashi, H., Sakai, K., Takeda, M., Kaneda, H., Nishio, K., & Nakagawa, K. (2016) · Lung Cancer · doi:10.1016/j.lungcan.2016.09.001 · Cited by 10 · see citing works
Self-citationDu, Z., Sun, J., Zhang, Y., Hesilaiti, N., Xia, Q., Cui, H., Fan, N., & Xu, X. (2023) · Biomolecules · doi:10.3390/biom13020210 · Cited by 9 · see citing works
Uncommon single and compound EGFR mutations: clinical outcomes of a heterogeneous subgroup of NSCLC
Rossi, S., Damiano, P., Toschi, L., Finocchiaro, G., Giordano, L., Marinello, A., Bria, E., D’Argento, E., & Santoro, A. (2021) · Current Problems in Cancer · doi:10.1016/j.currproblcancer.2021.100787 · Cited by 9 · see citing works
Qin, X., Gu, X., Lu, Y., & Zhou, W. (2018) · Cancer Management and Research · doi:10.2147/cmar.s174623 · Cited by 9 · see citing works
Gu, L., Huang, H., Xu, Z., Niu, X., Li, Z., Xia, L., Yu, Y., & Lü, S. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm12010236 · Cited by 8 · see citing works
Miura, S., Koh, Y., Azuma, K., Yoshioka, H., Koyama, K., Teraoka, S., Ishii, H., Kibata, K., Ozawa, Y., Tokito, T., et al. (2023) · BMC Cancer · doi:10.1186/s12885-022-10467-w · Cited by 8 · see citing works
Duan, H., Peng, Y., Cui, H., Qiu, Y., Li, Q., Zhang, J., Shen, W., Sun, C., & Luo, C. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s151125 · Cited by 8 · see citing works
Switching from first or Second Generation EGFR-TKI to Osimertinib in EGFR Mutation-Positive NSCLC
Imamura, F., Inoue, T., Kunimasa, K., Kubota, A., Kuhara, H., Tamiya, M., Nishino, K., Kimura, M., Kuno, K., Kawachi, H., et al. (2020) · Lung Cancer Management · doi:10.2217/lmt-2020-0005 · Cited by 8 · see citing works
Chen, L., Shih, J., Yu, C., & Yang, C. (2019) · Respirology Case Reports · doi:10.1002/rcr2.425 · Cited by 8 · see citing works
Wang, Z., Du, X., Chen, K., Li, S., Yu, Z., Wu, Z., Li, Y., Chen, D., & Liu, W. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.781084 · Cited by 7 · see citing works
Efficacy of osimertinib in a patient with leptomeningeal metastasis and EGFR uncommon S768I mutation
Okuno, T., Arakawa, S., Yoshida, T., & Ohe, Y. (2020) · Lung Cancer · doi:10.1016/j.lungcan.2020.03.016 · Cited by 7 · see citing works
Russo, A., Franchina, T., Ricciardi, G. R. R., & Adamo, V. (2017) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.09.132 · Cited by 7 · see citing works
Iida, Y., Kumasawa, F., Shimizu, T., Shintani, Y., Takahashi, N., & Gon, Y. (2019) · Thoracic Cancer · doi:10.1111/1759-7714.13269 · Cited by 6 · see citing works
Zhao, S., Cong, X., & Liu, Z. (2021) · BioMed Research International · doi:10.1155/2021/8817898 · Cited by 6 · see citing works
Sensitivity analysis of EGFR L861Q mutation to six tyrosine kinase inhibitors
Liu, C., Wang, Z., Liu, Q., Wu, G., Chu, C., Li, L., An, L., & Duan, S. (2022) · Clinical & Translational Oncology · doi:10.1007/s12094-022-02854-3 · Cited by 6 · see citing works
Biomarkers and Target Therapy for Lung Cancer
Shneider, O. V., Kamilova, Т. A., Голота, А. С., Sarana, А. М., & Sсherbak, S. G. (2021) · Physical and rehabilitation medicine medical rehabilitation · doi:10.36425/rehab63268 · Cited by 6 · see citing works
Wang, J., Huang, L., Chen, X., Yuan, Y., Sun, J., & Yang, M. (2022) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.c22-00303 · Cited by 5 · see citing works
Zhang, C., Lin, L. W., Zuo, R., Wang, Y., & Chen, P. (2020) · Thoracic Cancer · doi:10.1111/1759-7714.13606 · Cited by 5 · see citing works
Yu, L., Wang, R., Zhao, Y., Wu, Y., Wang, L., Chen, H., He, Z., Wang, Q., & Wu, Y. (2023) · Technology in Cancer Research & Treatment · doi:10.1177/15330338231168466 · Cited by 4 · see citing works
Behn, J., Deepak, R. N. V. K., Hu, J., & Fan, H. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.07.046 · Cited by 4 · see citing works
Liu, R., Zhou, J., & Ling, X. (2022) · Clinical Medicine Insights Oncology · doi:10.1177/11795549221103215 · Cited by 4 · see citing works
Ma, C., Wang, S., Mu, N., Li, J., Liu, M., Li, L., & Jiang, R. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01635 · Cited by 3 · see citing works
Qian, J., Ye, X., Huang, A., Qin, R., Cai, Y., Xue, Y., Zhang, S., Wang, W., Xiong, L., & Gu, A. (2022) · Journal of Thoracic Disease · doi:10.21037/jtd-22-507 · Cited by 3 · see citing works
Wu, G., Chen, Q., Lv, D., Lin, L., & Huang, J. (2023) · Recent Patents on Anti-Cancer Drug Discovery · doi:10.2174/1574892818666230316145232 · Cited by 3 · see citing works
[A Review of EGFR-TKIs Therapy of Non-small Cell Lung Cancer with Uncommon EGFR Mutations].
Du, W., Wo, Y., Lu, T., Wang, Y., & Jiao, W. (2019) · PubMed Central · doi:10.3779/j.issn.1009-3419.2019.09.07 · Cited by 3 · see citing works
Nagashima, H., Fukuhara, T., Utsumi, Y., Suzuki, A. S., Miyanaga, A., Seike, M., Azuma, K., Asahina, H., Kisohara, A., Kawashima, Y., et al. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.115693 · Cited by 2 · see citing works
Self-citationOiki, H., Suda, K., Hamada, A., Fujino, T., Obata, K., Kobayashi, Y., Sakai, K., Fukuda, S., Ohara, S., Ito, M., et al. (2025) · Cells · doi:10.3390/cells14171386 · Cited by 2 · see citing works
Self-citationHan, Y., Zhang, R., Lin, G., Zhang, K., Xie, J., & Li, J. (2017) · The Oncologist · doi:10.1634/theoncologist.2017-0042 · Cited by 2 · see citing works
Zhang, Y., Shen, J., Shao, L., Chen, Y., Lei, L., & Wang, J.-L. (2021) · World Journal of Clinical Cases · doi:10.12998/wjcc.v9.i27.8220 · Cited by 2 · see citing works
Gürsoy, P., Çakar, B., Ön, S., Göker, E., & Nart, D. (2022) · Turkish Thoracic Journal · doi:10.5152/turkthoracj.2022.21270 · Cited by 2 · see citing works
Cui, Q., Zhao, J., Ma, Y., Hu, Y., Ma, D., & Liu, H. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1714221 · Cited by 1 · see citing works
Minami, S., Ihara, S., Tanaka, T., Okada, H., Hashimoto, K., & Komuta, K. (2019) · Case Reports in Oncology · doi:10.1159/000497316 · Cited by 1 · see citing works
Molecular Pathology of Lung Tumors
Lo, Y., & Lindeman, N. I. (2023) · Springer eBooks · doi:10.1007/978-3-031-35118-1_9 · Cited by 1 · see citing works
Lin, R., Chen, R., Chen, Z., Hu, L., Guo, W., Zhang, Z., Lin, L., & Chen, H. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.731572 · Cited by 1 · see citing works
Nieva, J. J., Wang, X., Doroshow, D. B., Servidio, L., Cooper, M., Lau, Y. K., Karia, P. S., & Robichaux, J. P. (2025) · Oncology and Therapy · doi:10.1007/s40487-025-00395-7
Wang, Y., Ren, G., Song, Z., Hu, L., Li, W., & Wang, X. (2025) · Cancer Reports · doi:10.1002/cnr2.70444
Liu, S., Zhang, J., Dong, Y., & Wang, Y. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2025.1714432
Shi, H., Zhang, P., Chen, J., Li, H., Zhang, X. R., Zeng, B., Liu, T., & Zeng, T. (2026) · Cancer Medicine · doi:10.1002/cam4.71814
The Co-occurrence of EGFR Mutation and 16s rRNA in the Genome of Lung Cancer Patients
Sett, S., Dan, S., Alam, P., Dhara, P., Bera, R., Dey, S., De, T., Chakrabarti, J., Sengupta, S., Mandal, S., et al. (2026) · Journal of Current Oncological Trends · doi:10.4103/jcot.jcot_2_26
- Authors
- Banno, E., Togashi, Y., Nakamura, Y., Chiba, M., Kobayashi, Y., Hayashi, H., Terashima, M., de Velasco, M. A., Sakai, K., Fujita, Y., Mitsudomi, T., & Nishio, K.
- Affiliations
- Kindai University (JP)
- Department of Genome Biology Kindai University Faculty of Medicine Osaka‐Sayama Osaka Japan
- Corresponding author
- Nishio, Kazuto
- ORCID
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2016-07-14
- Volume
- 107
- Issue
- 8
- Pages
- 1134-1140
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC4982590
- OpenAlex
- W2409577054
- Cited by
- 87
- References
- 45
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 2 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 13 · 2019: 12 · 2018: 7 · 2017: 12 · 2016: 3
- FWCI
- 10.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Science (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15H06754)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- EGFR tyrosine kinase inhibitors, non-small cell lung cancer, drug sensitivity, afatinib, osimertinib, erlotinib, uncommon EGFR mutations
- MeSH terms
- Animals, Cell Line, Humans, Mutation, Transfection, Oncogene Proteins, Amino Acid Substitution, Inhibitory Concentration 50, Protein Kinase Inhibitors, Mutant Proteins, Mice, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
