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Cited by 132Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors

Open access
Kosaka, Takayuki, Tanizaki, Junko, Paranal, Raymond M., Endoh, Hideki, Lydon, Christine, Capelletti, Marzia, Repellin, Claire E., Choi, Jihyun +8 more·2017·Cancer Research
DOI 10.1158/0008-5472.can-16-3404PMC PMC5596996

Published version of a preprint

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Abstract

Insertion mutations in EGFR and HER2 both occur at analogous positions in exon 20. Non–small cell lung cancer (NSCLC) patients with tumors harboring these mutations seldom achieve clinical responses to dacomitinib and afatinib, two covalent quinazoline–based inhibitors of EGFR or HER2, respectively. In this study, we investigated the effects of specific EGFR and HER2 exon 20 insertion mutations from NSCLC patients that had clinically achieved a partial response after dacomitinib treatment. We identified Gly770 as a common feature among the drug-sensitive mutations. Structural modeling suggested that this mutation may facilitate inhibitor binding to EGFR. Introduction of Gly770 into two dacomitinib-resistant EGFR exon 20 insertion mutants restored sensitivity to dacomitinib. Based on these findings, we used afatinib to treat an NSCLC patient whose tumor harbored the HER2 V777_G778insGSP mutation and achieved a durable partial response. We further identified secondary mutations in EGFR (T790M or C797S) and HER2 (C805S) that mediated acquired drug resistance in drug-sensitive EGFR or HER2 exon 20 insertion models. Overall, our findings identified a subset of EGFR and HER2 exon 20 insertion mutations that are sensitive to existing covalent quinazoline–based EGFR/HER2 inhibitors, with implications for current clinical treatment and next-generation small-molecule inhibitors. Cancer Res; 77(10); 2712–21. ©2017 AACR.

Integrity signals

Registry

Crossref · 10.1158/0008-5472.can-16-3404

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 28 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    HER2 mutant Ba/F3 cells were generally more sensitive to neratinib, dacomitinib, and afatinib than EGFR exon 20 mutant Ba/F3 cells.

    “In general, the HER2 mutant Ba/F3 cells were more sensitive to all three drugs compared to the EGFR exon 20 mutant Ba/F3 cells (Figure 1A and Figure S1).”
    Quote in the paperSubstantial claim
  • Findingcitation

    One patient with the D770delinsGY EGFR mutation showed a partial response to dacomitinib.

    “Some of these patients were enrolled in clinical trials of dacomitinib treatment, and one patient with D770delinsGY showed partial response (25).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Janne, 2011, Phase I dose-escalation study of the pan-HER inhibitor, PF299804, in patients with advanced malignant solid tumors, Clin Cancer Res source

      Not checked in the free run.

  • Findingnone given

    The HER2 V777_G778insGSP mutation causes the same protein changes as the HER2 P780_Y781insGSP mutation.

    “The HER2 V777_G778insGSP mutation leads to the same changes in the HER2 protein as does the HER2 P780_Y781insGSP mutation (Table 2).”
    Quote in the paperSubstantial claim
  • Findingown data

    Immunoblot analyses showed that inhibition of HER2 phosphorylation corresponded to the relative cellular sensitivities for each tested drug.

    “Immunoblot analyses demonstrating inhibition of HER2 phosphorylation corresponded to the relative cellular sensitivities for each of the tested drugs (Figure 1D).”
    Quote in the paperSubstantial claim
  • Findingown data

    Ba/F3 cells harboring InsCPG were similarly sensitive to all three covalent inhibitors.

    “Ba/F3 cells harboring the InsCPG were similarly sensitive to all three covalent inhibitors (Figure 1C).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 29
  • The quote only partly states this claim. 2
  • Classified as probably not a substantial claim. 2

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    InsYVMA Ba/F3 cells were more sensitive to neratinib than to other drugs, although not as sensitive as WT HER2 cells.

    “These cells were more sensitive to neratinib although not as sensitive as those the WT HER2 cells (Figure 1C).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Both the H773_V774 insH and D770_N771 insSVD mutants transformed Ba/F3 cells and supported IL-3-independent growth.

    “Both mutants led to transformation and IL-3 independent growth (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    DFCI58 was established from the adenocarcinoma of a 60-year-old male with stage IV disease and an EGFR H773_V774insNPH exon 20 mutation.

    “DFCI58 was established from the adenocarcinoma of a 60-year-old male. He was diagnosed with stage IV disease and and an EGFR H773_V774insNPH exon 20 mutation was identified.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    InsGY Ba/F3 cells were slightly more sensitive to afatinib, while all five EGFR exon 20 insertion mutations were relatively more resistant to neratinib.

    “The InsGY Ba/F3 cells were also slightly more sensitive to afatinib while all five exon 20 insertion mutations were relatively more resistant to neratinib.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The patient's response to afatinib lasted 7 months, with progression due to leptomeningeal carcinomatosis.

    “The response was sustained for 7 months with eventual clinical progression due to leptomeningeal carcinomatosis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Forty-four EGFR exon 20 insertion mutations were identified, representing 7% of EGFR mutant cases and 1.7% of all tested cases.

    “Forty four EGFR mutations were insertion mutations in exon 20 (7% of EGFR mutant cases and 1.7% of all tested cases).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Substituting alanine, arginine, or aspartic acid for the inserted glycine in D770delinsGY did not uniformly confer resistance; alanine was slightly more resistant, while arginine and aspartic acid increased sensitivity.

    “Notably, contrary to our hypothesis, these substitutions did not uniformly confer resistance; the alanine mutant was slightly more resistant while the arginine and aspartic acid mutants exhibited increased sensitivity (Figure 2D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Arg776 interaction site is accessible in wild-type EGFR but is blocked by Asp770 in the insertion mutant.

    “While this position is accessible in wild type EGFR, it is blocked by Asp770 in the insertion mutant (Figure 2C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    InsYVMA Ba/F3 cells were the most resistant among HER2 mutants, with IC50 values higher than WT HER2.

    “The InsYVMA Ba/F3 cells were the most resistant with IC50 values higher than that seen for WT HER2 (Figure 1C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the DFCI cohort, 2789 patients were tested for EGFR mutations between 2004 and 2015, and 1901 patients were tested for HER2 mutations between 2009 and 2015.

    “Between 2004 and 2015, 2789 patients were tested for EGFR mutations and between 2009 and 2015, 1901 patients were tested for HER2 mutations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    All EGFR exon 20 insertion-containing Ba/F3 cells were resistant to gefitinib, while EGFR WT cells remained sensitive.

    “All of the EGFR exon 20 insertion containing Ba/F3 cells were resistant to gefitinib while the EGFR WT cells remained sensitive (data not shown).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Two patients with P780_Y781insGSP and one patient with M774delinsWLV achieved a partial response to dacomitinib.

    “Some HER2 exon 20 patients were also enrolled into clinical trials of dacomitinib, and two patients with a P780_Y781insGSP and one patient with a M774delinsWLV achieved a partial response (26).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Kris, 2015, Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors, Ann Oncol source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    DFCI127 was established from the adenocarcinoma of a 42-year-old female with stage IV disease and an EGFR P772_H773insPNP exon 20 mutation.

    “DFCI127 was established from the adenocarcinoma of a 42-year-old female. She was diagnosed with stage IV disease and had an EGFR P772_H773insPNP exon 20 mutation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Five of the 8 HER2 exon 20 variants were detected only once.

    “Five of the 8 variants were detected only once.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The patient experienced significant tumor shrinkage and decreased supplemental oxygen requirement after afatinib.

    “She experienced significant tumor shrinkage (Figure 3), accompanied by a decrease in the requirement for supplemental oxygen.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All EGFR exon 20 mutant Ba/F3 cells grew without IL-3, except EGFR WT Ba/F3 cells, which required EGF.

    “All exon 20 EGFR mutant Ba/F3 cells were able to grow without interleukin-3 (IL-3) with the exception of EGFR WT Ba/F3 cells which required 10 ng/ml of EGF to sustain growth (data not shown).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In soft agar colony formation assays, neratinib was most effective at inhibiting growth of InsGSP and InsYVMA colonies, while dacomitinib was most effective against InsWLV cells.

    “Similar to the Ba/F3 cells, neratinib was most effective at inhibiting the growth of the InsGSP and InsYVMA colonies while dacomitinib was most effective against the InsWLV cells (Figures S2A and S2B).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Dacomitinib was a more potent inhibitor of WT EGFR Ba/F3 cells than of EGFR exon 20 insertion mutant Ba/F3 cells.

    “Dacomitinib was a more potent inhibitor of WT EGFR Ba/F3 cells (Figure 1A and Figure S1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The most common EGFR exon 20 insertion was D770_N771insSVD, the second most common was V769_D770insASV, and together they accounted for 36.3% (16/44) of all EGFR exon 20 insertions.

    “The most common one was a duplication of codon 768 to 770 resulting in D770_N771insSVD. The second most common one was a duplication of codon 767 to 769 resulting in V769_D770insASV. These two insertions are very similar in their locations and together accounted for 36.3% (16 in 44 cases) of all EGFR exon 20 insertions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Seventeen drug-resistant clones were obtained from EGFR exon 20 InsGY cells after ENU exposure and selection with 100 nM or 1 μM dacomitinib; 12 from 100 nM and 5 from 1 μM.

    “Seventeen (17) drug resistant clones were expanded and identified to be drug resistant; 12 from the 100 nM and 5 from the 1 μM treated cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Forty-seven HER2 exon 20 mutations were detected, representing 2.5% of all tested cases.

    “Forty seven HER2 mutations were detected in exon 20 (2.5% of all tested cases).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Three of these sensitive mutations came from patients who clinically responded to dacomitinib, and the fourth was an in vitro mutation conferring drug sensitivity.

    “Three of these mutations were initially identified from the tumors of lung cancer patients who had clinically responded to dacomitinib while the fourth was identified as an in vitro mutation conferring drug sensitivity (Figure 1C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    HER2 mutations from dacomitinib-responding patients were the most sensitive to dacomitinib in vitro, but the IC50 differences from non-responding mutations such as HER2 InsYVMA were less pronounced than for EGFR exon 20 mutations.

    “The HER2 mutations identified from dacomitinib responding patients were also the most sensitive to dacomitinib in vitro (Figure 1C) but the differences in the IC50 values between these and mutations from patients with no response (such as HER2 InsYVMA) were not as pronounced as in those with the EGFR exon 20 mutations (Figure 1C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In a review of 84 patients with EGFR exon 20 insertions treated with gefitinib or erlotinib, the response rate was 11% and progression-free survival was 2.4 months.

    “A review of 84 patients with exon 20 insertions across different series treated with either gefitinib or erlotinib demonstrated a RR of only 11% with a PFS of 2.4 months (12).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Naidoo, 2015, Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response to erlotinib, Cancer source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Afatinib treatment in EGFR exon 20 insertion patients is associated with a low response rate of 8.7% and progression-free survival of 2.7 months.

    “Similarly, treatment with afatinib in this patient population is also associated with a low RR and PFS (8.7% and 2.7 months, respectively) (13).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Yang, 2015, 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 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HER2 mutations are oncogenic in vitro and in vivo.

    “Mutations in HER2 are oncogenic both in vitro and in vivo (14–16).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [14] Shimamura, 2006, Non-small-cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272, Cancer Res source

      Not checked in the free run.

    • cites [15] Wang, 2006, HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors, Cancer Cell source

      Not checked in the free run.

    • cites [16] Perera, 2009, HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ENU mutagenesis has previously identified clinically relevant drug resistance mutations to EGFR TKIs.

    “This approach has previously led to identification of clinically relevant drug resistance mutations to EGFR TKIs (30, 31).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [30] Zhou, 2009, Novel mutant-selective EGFR kinase inhibitors against EGFR T790M, Nature source

      Not checked in the free run.

    • cites [31] Ercan, 2015, EGFR mutations and resistance to irreversible pyrimidine based EGFR inhibitors, Clin Cancer Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Only one crystal structure is available for an exon 20 variant (insNPG), and it reveals an inhibitor binding site essentially indistinguishable from that of the inhibitor-sensitive L858R mutant.

    “Only one crystal structure is available for an exon 20 variant (the insNPG mutant) and it reveals an inhibitor binding site that is essentially indistinguishable from that of the inhibitor-sensitive L858R mutant (8).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Yasuda, 2013, Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer, Sci Transl Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a randomized phase II trial, no HER2 mutation-positive NSCLC patients responded to neratinib alone, while 3 of 14 (21%) treated with neratinib plus temsirolimus had a partial response.

    “While none of the patients treated with neratinib alone responded (RR: 0%), 3 of 14 (RR: 21%) patients treated with the combination of neratinib/temsirolimus had a PR (23).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Besse, 2014, Neratinib (N) with or without temsirolimus (TEM) in patients (pts) with non-small cell lung cancer (NSCLC) carrying HER2 somatic mutations: an international randomized phase II study, Ann Oncol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Previous studies identified EGFR A763_Y764insFQEA as sensitive to erlotinib, while most EGFR exon 20 mutations are resistant to EGFR inhibitors.

    “Although the vast majority are associated with resistance to EGFR inhibitors, previous studies have identified a unique EGFR exon 20 mutation (A763_Y764insFQEA) that remained sensitive to erlotinib (8).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Yasuda, 2013, Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer, Sci Transl Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Glycine mutations can restore inhibitor sensitivity without abrogating transforming activity.

    “Indeed, glycine mutations can restore inhibitor sensitivity without abrogating transforming activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Cells with an EGFR activating mutation and C797S without T790M are resistant to mutant-selective EGFR inhibitors (WZ4002, osimertinib, rociletinib) but remain sensitive to afatinib.

    “Cells expressing an EGFR activating mutation and C797S in the absence of T790M are resistant to mutant selective EGFR inhibitors (WZ4002, osimertinib and rociletinib) but remain sensitive to afatinib (31).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Ercan, 2015, EGFR mutations and resistance to irreversible pyrimidine based EGFR inhibitors, Clin Cancer Res source

      Not checked in the free run.

    • Rests on an assumption: EGFR C797 is the covalent binding site for neratinib, dacomitinib, and afatinib.
32 of 32

  • The paper relies on this without support.

    EGFR exon 20 insertion mutations and HER2 exon 20 insertion mutations occur at structurally analogous positions.

    “Insertion mutations in EGFR and HER2 both occur at analogous positions in exon 20.”
    “Notably, EGFR exon 20 insertion mutations occur in a structurally analogous position as exon 20 insertion mutations in HER2.”

  • The paper relies on this without support.

    EGFR C797 is the covalent binding site for neratinib, dacomitinib, and afatinib.

    “EGFR C797 is the site of covalent binding of neratinib, dacomitinib and afatinib.”

  • The paper relies on this without support.

    There are currently no effective or approved targeted therapies for patients with EGFR or HER2 exon 20 mutant lung tumors.

    “Lung cancer patients harboring EGFR or HER2 exon 20 mutant tumors represent a unique subset of patients for whom there are currently no effective or approved targeted therapies.”

  • The paper relies on this without support.

    No features among EGFR or HER2 exon 20 mutations have been identified that predict clinical sensitivity to existing covalent EGFR/HER2 inhibitors.

    “To date, no features among the different EGFR or HER2 exon 20 mutations have been identified that could predict clinical sensitivity to existing covalent EGFR or HER2 inhibitors.”

  • The paper relies on this without support.

    The common EGFR exon 20 mutations InsSVD and InsASV account for about one-third of all exon 20 mutations, and HER2 InsYVMA accounts for about two-thirds of HER2 exon 20 mutations.

    “Furthermore, there continues to be a need to develop effective therapies for patients with the more common EGFR exon 20 mutation (InsSVD and InsASV, accounting for ~ 1/3 of all exon 20 mutations) and HER2 exon 20 mutations (InsYVMA, accounting for ~ 2/3 of all exon 20 mutations).”
5 of 5

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?

  • The frequency and effects of atypical EGFR mutations on drug sensitivity are unknown.

    “Furthermore, the frequency and effects of atypical EGFR mutations on drug sensitivity are unknown1,3,7–10.”

    From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [10]

  • Patients with atypical EGFR mutations show heterogeneous and reduced responses to EGFR inhibitors, including osimertinib.

    “Patients with atypical EGFR mutations show heterogeneous and reduced responses to EGFR inhibitors1,3,7–10, including osimertinib12.”

    From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [10]

  • In a recent study of rare EGFR and HER2 exon 20 mutations, heterogeneous response to covalent quinazoline-based second-generation inhibitors was found; concentrations required to target more common exon 20 insertion mutations were above clinically achievable.

    “In a recent study of rare EGFR and HER2 exon 20 mutations, the authors found a heterogeneous response to covalent quinazoline-based second-generation inhibitors, such as dacomitinib and afatinib; however, the concentrations that were required to target more common exon 20 insertion mutations were above what are clinically achievable24.”

    From Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer (2018) · cites this paper as [24]

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.

  • HER2 exon 20 case totals disagree

    Minor

    The results first give 47 HER2 exon 20 cases, then use 48 as the total for the same group.

  • EGFR insertion prevalence is overstated

    Minor

    Forty-four cases among 2,789 tested patients is approximately 1.58%, which rounds to 1.6%, not the reported 1.7%.

    Reported 1.7 · recomputed 1.577626

  • Wild-type HER2 is counted as an insertion mutant

    Minor

    The six cell lines comprise wild-type HER2 and five insertion mutants, so they cannot all be HER2 exon 20 insertion mutant cell lines.

3 of 3

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Related

Authors
Kosaka, T., Tanizaki, J., Paranal, R. M., Endoh, H., Lydon, C., Capelletti, M., Repellin, C. E., Choi, J., Ogino, A., Calles, A., Ercan, D., Redig, A. J., Bahcall, M., Oxnard, G. R., Eck, M. J., & Jänne, P. A.
Affiliations
  • Harvard University (US)
  • 1Lowe Center for Thoracic Oncology, Harvard Medical School, Boston, Massachusetts.
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2017-05-14
Volume
77
Issue
10
Pages
2712-2721
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-16-3404
PMC
PMC5596996
OpenAlex
W2598622710
Cited by
131
References
33
Citations by year
2026: 5 · 2025: 4 · 2024: 7 · 2023: 18 · 2022: 17 · 2021: 22 · 2020: 12 · 2019: 16 · 2018: 23 · 2017: 7
FWCI
13.12
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NCI (R01CA135257, R01CA114465)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
EGFR exon 20 insertion, HER2 exon 20 insertion, non-small cell lung cancer, dacomitinib, afatinib, acquired drug resistance, T790M, C797S, structural modeling, drug sensitivity
MeSH terms
Adult, Animals, Antineoplastic Agents, Codon, Disease Models, Animal, Dose-Response Relationship, Drug, Exons, Female, Humans, Lung Neoplasms, Male, Middle Aged, Models, Molecular, Molecular Conformation, Protein Binding, Tomography, X-Ray Computed, Gene Expression, Mutagenesis, Insertional, Treatment Outcome, Erb-b2 Receptor Tyrosine Kinases, Drug Resistance, Neoplasm, Amino Acid Substitution, Xenograft Model Antitumor Assays, Cell Line, Tumor, Protein Kinase Inhibitors, Mice, ErbB Receptors

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