The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer
Open accessAbstract
Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“Inhibition of the FGFR signaling pathway reduces ERK and mTOR activation, whereas AXL inhibition attenuates the activation of PI3K pathway [43, 136–139].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [43]
In the citing paper
“High feedback activation of the FGFR/AXL signaling pathway was found in mesenchymal cells.”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [43]
In the citing paper
“In the context of an EMT, AXL upregulation appears as a novel mechanism of acquired EGFR-TKI resistance in EGFR-mutant NSCLCs.”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [40]
In the citing paper
“Therefore, an EMT-associated transcriptional programme involving upregulation of vimentin may, in part, drive AXL overexpression in EGFR-mutant lung cancer cells with acquired EGFR-TKI resistance.40”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [40]
In the citing paper
“Pharmacological inhibition of AXL significantly decreased the proliferative and invasive abilities of cancer cells and increased their chemosenstivity through inhibition of AKT and MAPK pathways.”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [40]
In the citing paper
“Rare EGFR point mutations (<10% of patients) that result in resistance include Asp761Tyr,39 Thr854Ala,40 and Leu747Ser. The mechanism (or mechanisms) underlying resistance conferred by these mutations is still unclear.”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [40]
In the citing paper
“Recently, an integrated analysis in human EGFR-mutant NSCLC models and in a large clinical cohorts of paired NSCLC specimens from EGFR-TKI-treated patients demonstrated an upregulation of AXL tyrosine kinase receptor or of its ligand, GAS6, in resistant samples.”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [40]
In the citing paper
“We observed an AXL mutation in one case with acquired T790M/C797S (Pt. 12 Supple Table 2)[24], suggesting association with EMT.”
From Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in EGFR -Mutant NSCLC (2018) · cites this paper as [24]
In the citing paper
“AXL inhibition has been reported to sensitize drug-resistant mesenchymal tumor cells to anticancer agents, including antimitotic agents, epidermal growth factor receptor (EGFR) inhibitors, and PI3K inhibitors”
From Hypoxic control of metastasis (2016) · cites this paper as [84]
In the citing paper
“Finally, in erlotinib-resistant EGFR mutant lung cancer cells and lapatinib-resistant HER2-amplified breast cancer cells, levels of the AXL RTK were markedly increased (Liu et al., 2009; Zhang et al., 2012).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Zhang et al., 2012
In the citing paper
“Targeting AXL was able to re-sensitize some of these resistant cancers to the original TKI.”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Zhang et al., 2012
In the citing paper
“In similar examples of resistance mediated by IGF-IR and AXL, inhibition of the bypass RTK in combination with the EGFR is needed to overcome resistance (Cortot et al., 2013; Guix et al., 2008; Zhang et al., 2012).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Zhang et al., 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486
EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
Self-citationMET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338
Self-citationEGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964
Self-citationPao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., Kris, M. G., & Varmus, H. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020073 · Cited by 3,527
Self-citationGenotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499
Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
Polyak, K., & Weinberg, R. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2620 · Cited by 3,302
The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
Yun, C.-H., Mengwasser, K. E., Toms, A. V., Woo, M. S., Greulich, H., Wong, K.-K., Meyerson, M., & Eck, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709662105 · Cited by 2,118
Gefitinib-Sensitizing EGFR Mutations in Lung Cancer Activate Anti-Apoptotic Pathways
Sordella, R., Bell, D. W., Haber, D. A., & Settleman, J. E. (2004) · Science · doi:10.1126/science.1101637 · Cited by 1,605
Cited by
Sorted by citations
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944
Cancer drug resistance: an evolving paradigm
Holohan, C., Van Schaeybroeck, S., Longley, D. B., & Johnston, P. G. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3599 · Cited by 4,681
EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
Shibue, T., & Weinberg, R. A. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.44 · Cited by 2,539
Yu, H. A., Arcila, M. E., Rekhtman, N., Sima, C. S., Zakowski, M. F., Pao, W., Kris, M. G., Miller, V. A., Ladanyi, M., & Riely, G. J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2246 · Cited by 2,454
Self-citationEpidermal Growth Factor Receptor Cell Proliferation Signaling Pathways
Wee, P., & Wang, Z. (2017) · Cancers · doi:10.3390/cancers9050052 · Cited by 2,027
Non-small-cell lung cancers: a heterogeneous set of diseases
Chen, Z., Brainson, C. F., Hammerman, P. S., Kim, C. F., & Wong, K. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3775 · Cited by 1,973
Liquid biopsy: monitoring cancer-genetics in the blood
Crowley, E. H., Nicolantonio, F. D., Loupakis, F., & Bardelli, A. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.110 · Cited by 1,857
Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA
Murtaza, M., Dawson, S.-J., Tsui, D. W. Y., Gale, D., Forshew, T., Piskorz, A. M., Parkinson, C., Chin, S.-F., Kingsbury, Z., Wong, A. S. C., et al. (2013) · Nature · doi:10.1038/nature12065 · Cited by 1,624
Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340
Gridelli, C., Rossi, A., Carbone, D. P., Guarize, J., Karachaliou, N., Mok, T. S. K., Petrella, F., Spaggiari, L., & Rosell, R. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.9 · Cited by 1,146
Self-citationByers, L. A., Diao, L., Wang, J., Saintigny, P., Girard, L., Peyton, M., Shen, L., Fan, Y., Giri, U., Tumula, P. K., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1558 · Cited by 1,059
Self-citationThe quest to overcome resistance to EGFR-targeted therapies in cancer
Chong, C. R., & Janne, P. A. (2013) · Nature Medicine · doi:10.1038/nm.3388 · Cited by 1,076
ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
Arteaga, C. L., & Engelman, J. A. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.025 · Cited by 1,048
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009
Understanding and targeting resistance mechanisms in NSCLC
Rotow, J. K., & Bivona, T. G. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.84 · Cited by 997
Self-citationAcquired resistance to TKIs in solid tumours: learning from lung cancer
Camidge, D. R., Pao, W., & Sequist, L. V. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.104 · Cited by 862
Wu, S., & Shih, J. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0777-1 · Cited by 802
Dynamic EMT: a multi‐tool for tumor progression
Brabletz, S., Schuhwerk, H., Brabletz, T., & Stemmler, M. P. (2021) · The EMBO Journal · doi:10.15252/embj.2021108647 · Cited by 800
Cell death-based treatment of lung adenocarcinoma
Denisenko, T. V., Budkevich, I. N., & Zhivotovsky, B. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0063-y · Cited by 768
Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors
Westover, D., Zugazagoitia, J., Cho, B. C., Lovly, C. M., & Paz-Ares, L. (2018) · Annals of Oncology · doi:10.1093/annonc/mdx703 · Cited by 766
The great escape: tumour cell plasticity in resistance to targeted therapy
Boumahdi, S., & de Sauvage, F. J. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0044-1 · Cited by 785
Targeted therapy for non-small cell lung cancer: current standards and the promise of the future.
(2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2218-6751.2014.05.01 · Cited by 716
The TAM family: phosphatidylserine-sensing receptor tyrosine kinases gone awry in cancer
Graham, D. K., DeRyckere, D., Davies, K. D., & Earp, H. S. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3847 · Cited by 717
Lim, Z.-F., & Ma, P. C. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0818-2 · Cited by 658
Self-citationWalter, 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
EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance
Uribe, M. L., Marrocco, I., & Yarden, Y. (2021) · Cancers · doi:10.3390/cancers13112748 · Cited by 604
TAM receptors regulate multiple features of microglial physiology
Fourgeaud, L., Través, P. G., Tufail, Y., Leal-Bailey, H., Lew, E. D., Burrola, P. G., Callaway, P., Zagórska, A., Rothlin, C. V., Nimmerjahn, A., et al. (2016) · Nature · doi:10.1038/nature17630 · Cited by 600
Lemke, G. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009076 · Cited by 598
Mechanisms of resistance to EGFR tyrosine kinase inhibitors
Huang, L., & Fu, L. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.07.001 · Cited by 596
Blakely, C. M., Watkins, T. B. K., Wu, W., Gini, B., Chabon, J. J., McCoach, C. E., McGranahan, N., Wilson, G. A., Birkbak, N. J., Olivas, V. R., et al. (2017) · Nature Genetics · doi:10.1038/ng.3990 · Cited by 571
Self-citationTargeting ALK: Precision Medicine Takes on Drug Resistance
Lin, J. J., Riely, G. J., & Shaw, A. T. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1123 · Cited by 532
A Melanoma Cell State Distinction Influences Sensitivity to MAPK Pathway Inhibitors
Konieczkowski, D. J., Johannessen, C. M., Abudayyeh, O. O., Kim, J. W., Cooper, Z. A., Piris, A., Frederick, D. T., Barzily-Rokni, M., Straussman, R., Haq, R., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0424 · Cited by 553
Mak, M. P., Tong, P., Diao, L., Cardnell, R. J., Gibbons, D. L., William, W. N., Skoulidis, F., Parra, E. R., Rodriguez‐Canales, J., Wistuba, I. I., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0876 · Cited by 540
Rational combinations of targeted cancer therapies: background, advances and challenges
Jin, H., Wang, L., & Bernards, R. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00615-z · Cited by 503
New and emerging targeted treatments in advanced non-small-cell lung cancer
Hirsch, F. R., Suda, K., Wiens, J., & Bunn, P. A. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31473-8 · Cited by 497
Mechanisms of resistance to EGFR-targeted drugs: lung cancer
Morgillo, F., Della Corte, C. M., Fasano, M., & Ciardiello, F. (2016) · ESMO Open · doi:10.1136/esmoopen-2016-000060 · Cited by 476
Kurppa, K. J., Liu, Y., To, C., Zhang, T., Fan, M., Vajdi, A., Knelson, E. H., Xie, Y., Lim, K., Cejas, P., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2019.12.006 · Cited by 475
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor–Resistant Disease
Ohashi, K., Maruvka, Y. E., Michor, F., & Pao, W. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.3912 · Cited by 467
Yuan, S., Norgard, R. J., & Stanger, B. Z. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0015 · Cited by 491
Institutional implementation of clinical tumor profiling on an unselected cancer population
Sholl, L. M., Do, K., Shivdasani, P., Cerami, E., Dubuc, A. M., Kuo, F. C., Garcia, E. P., Jia, Y., Davineni, P., Abo, R. P., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.87062 · Cited by 450
Tumour heterogeneity and the evolution of polyclonal drug resistance
Burrell, R. A., & Swanton, C. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.06.005 · Cited by 435
EGFR-TKIs resistance via EGFR-independent signaling pathways
Liu, Q., Yu, S., Zhao, W., Qin, S., Chu, Q., & Wu, K. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0793-1 · Cited by 424
Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma
Zhou, L., Liu, X.-D., Sun, M., Zhang, X., German, P., Bai, S., Ding, Z., Tannir, N. M., Wood, C. G., Matin, S. F., et al. (2015) · Oncogene · doi:10.1038/onc.2015.343 · Cited by 400
Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer
Tan, C., Gilligan, D., & Pacey, S. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00246-6 · Cited by 393
Le, X., Puri, S., Negrao, M. V., Nilsson, M. B., Robichaux, J., Boyle, T., Hicks, J. K., Lovinger, K. L., Roarty, E., Rinsurongkawong, W., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1542 · Cited by 387
Self-citationExosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer
Kim, D. H., Kim, H., Choi, Y. J., Kim, S. Y., Lee, J.-E., Sung, K. J., Sung, Y. H., Pack, C., Jung, M., Han, B., et al. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0295-2 · Cited by 399
Self-citationAn integrin β3-KRAS-RalB complex drives tumour stemness and resistance to EGFR inhibition
Seguin, L., Kato, S., Franovic, A., Camargo, M. F., Lesperance, J., Elliott, K. C., Yebra, M., Mielgo, A., Lowy, A. M., Husain, H., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb2953 · Cited by 374
AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells
Taniguchi, H., Yamada, T., Wang, R., Tanimura, K., Adachi, Y., Nishiyama, A., Tanimoto, A., Takeuchi, S., Araujo, L. H., Boroni, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08074-0 · Cited by 372
Liu, X., Jia, Y., Stoopler, M. B., Shen, Y., Cheng, H., Chen, J., MANSUKHANI, M. M., Koul, S., Halmos, B., & Borczuk, A. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.62.0674 · Cited by 350
Self-citationSundaresan, T. K., Sequist, L. V., Heymach, J. V., Riely, G. J., Jänne, P. A., Koch, W. H., Sullivan, J. P., Fox, D. B., Maher, R., Muzikansky, A., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1031 · Cited by 347
Pleiotropic Roles for ZEB1 in Cancer
Caramel, J., Plaschka, M., & Puisieux, A. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-2476 · Cited by 342
Giving AXL the axe: targeting AXL in human malignancy
Gay, C. M., Balaji, K., & Byers, L. A. (2017) · British Journal of Cancer · doi:10.1038/bjc.2016.428 · Cited by 346
Distinctive properties of metastasis-initiating cellsPreprint
Celià-Terrassa, T., & Kang, Y. (2016) · Genes & Development · doi:10.1101/gad.277681.116 · Cited by 342
Elkabets, M., Pazarentzos, E., Juric, D., Sheng, Q., Pelossof, R. A., Brook, S., Benzaken, A. O., Rodon, J., Morse, N., Yan, J. J., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.010 · Cited by 325
Self-citationA perspective on anti-EGFR therapies targeting triple-negative breast cancer.
Nakai, K., Hung, M., & Yamaguchi, H. (2016) · Europe PMC (PubMed Central) · Cited by 324
Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or next-generation TKI?
Recondo, G., Facchinetti, F., Olaussen, K. A., Besse, B., & Friboulet, L. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0081-4 · Cited by 321
Yang, Y., Li, S., Wang, Y., Zhao, Y., & Li, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01168-8 · Cited by 327
Bhat, G. R., Sethi, I., Sadida, H. Q., Rah, B., Mir, R., Algehainy, N. A., Albalawi, I. A., Masoodi, T., Subbaraj, G. K., Jamal, F., et al. (2024) · Cancer and Metastasis Reviews · doi:10.1007/s10555-024-10172-z · Cited by 330
Stewart, E., Tan, S. Z., Liu, G., & Tsao, M. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2218-6751.2014.11.06 · Cited by 314
Genetics and biomarkers in personalisation of lung cancer treatment
Rosell, R., Bivona, T. G., & Karachaliou, N. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61715-8 · Cited by 305
Self-citationPersistent Cancer Cells: The Deadly Survivors
Shen, S., Vagner, S., & Robert, C. (2020) · Cell · doi:10.1016/j.cell.2020.10.027 · Cited by 320
Receptor Tyrosine Kinase-Targeted Cancer Therapy
Yamaoka, T., Kusumoto, S., Ando, K., Ohba, M., & Ohmori, T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113491 · Cited by 297
Lim, S. M., Syn, N. L. X., Cho, B. C., & Soo, R. A. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.02.006 · Cited by 293
Meyer, A. S., Miller, M. A., Gertler, F. B., & Lauffenburger, D. A. (2013) · Science Signaling · doi:10.1126/scisignal.2004155 · Cited by 283
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 307
Antitumour immunity regulated by aberrant ERBB family signalling
Kumagai, S., Koyama, S., & Nishikawa, H. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-020-00322-0 · Cited by 284
Emerging role of tumor cell plasticity in modifying therapeutic response
Qin, S., Jiang, J., Lü, Y., Nice, E. C., Huang, C., Zhang, J., & He, W. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00313-5 · Cited by 289
Differential TAM receptor–ligand–phospholipid interactions delimit differential TAM bioactivities
Lew, E. D., Oh, J., Burrola, P., Lax, I., Zagórska, A., Través, P. G., Schlessinger, J., & Lemke, G. (2014) · eLife · doi:10.7554/elife.03385 · Cited by 281
Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET
Rankin, E. B., Fuh, K. C., Castellini, L., Viswanathan, K., Finger, E. C., Diep, A. N., LaGory, E. L., Kariolis, M. S., Chan, A., Lindgren, D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404848111 · Cited by 269
Shien, K., Toyooka, S., Yamamoto, H., Soh, J., Jida, M., Thu, K. L., Hashida, S., Maki, Y., Ichihara, E., Asano, H., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4136 · Cited by 273
Plasticity of tumour and immune cells: a source of heterogeneity and a cause for therapy resistance?
Hölzel, M., Bovier, A., & Tüting, T. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3498 · Cited by 275
Aissa, A. F., Islam, A. B. M. M. K., Ariss, M., Go, C. C., Rader, A. E., Conrardy, R. D., Gajda, A. M., Rubio-Pérez, C., Valyi‐Nagy, K., Pasquinelli, M. M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21884-z · Cited by 278
Misale, S., Arena, S., Lamba, S., Siravegna, G., Lallo, A., Hobor, S., Russo, M., Buscarino, M., Lazzari, L., Sartore-Bianchi, A., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007947 · Cited by 263
Bypass Mechanisms of Resistance to Receptor Tyrosine Kinase Inhibition in Lung Cancer
Niederst, M. J., & Engelman, J. A. (2013) · Science Signaling · doi:10.1126/scisignal.2004652 · Cited by 268
A Convergence-Based Framework for Cancer Drug Resistance
Konieczkowski, D. J., Johannessen, C. M., & Garraway, L. A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.025 · Cited by 258
Woolston, A., Khan, K., Spain, G., Barber, L. J., Griffiths, B., Gonzalez-Exposito, R., Hornsteiner, L., Punta, M., Patil, Y., Newey, A., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.05.013 · Cited by 254
Nagano, T., TACHIHARA, M. Y., & Nishimura, Y. (2018) · Cells · doi:10.3390/cells7110212 · Cited by 259
Ware, K. E., Hinz, T. K., Kleczko, E. K., Singleton, K. R., Marek, L. A., Helfrich, B., Cummings, C. T., Graham, D. K., Astling, D. P., Tan, A. C., et al. (2013) · Oncogenesis · doi:10.1038/oncsis.2013.4 · Cited by 254
Adachi, Y., Ito, K., Hayashi, Y., Kimura, R., Tan, T. Z., Yamaguchi, R., & Ebi, H. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2077 · Cited by 249
Circulating Tumor DNA as Biomarkers for Cancer Detection
Han, X., Wang, J., & Sun, Y. (2017) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.12.004 · Cited by 246
PTEN and PI3K/AKT in Non-Small-Cell Lung Cancer
Pérez-Ramírez, C., Cañadas‐Garre, M., Molina‐Vila, M. Á., Faus-Dáder, M. J., & Calleja‐Hernández, M. Á. (2015) · Pharmacogenomics · doi:10.2217/pgs.15.122 · Cited by 246
Li, L., Han, R., Xiao, H., Lin, C., Wang, Y., Liu, H., Li, K., Chen, H., Sun, F., Yang, Z., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2613 · Cited by 240
Fibronectin in Cancer: Friend or Foe
Lin, T.-C., Yang, C.-H., Cheng, L.-H., Chang, W., Lin, Y.-R., & Cheng, H.-C. (2019) · Cells · doi:10.3390/cells9010027 · Cited by 241
Resisting Resistance: Targeted Therapies in Lung Cancer
Lin, J. J., & Shaw, A. T. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.05.010 · Cited by 241
Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Zhu, C., Guan, X., Zhang, X., Luan, X., Song, Z., Cheng, X., Zhang, W., & Qin, J.-J. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01629-2 · Cited by 231
Update on Epithelial-Mesenchymal Plasticity in Cancer Progression
Fontana, R., Mestre‐Farrera, A., & Yang, J. (2023) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-051222-122423 · Cited by 241
Costa, C., Molina, M. A., Drozdowskyj, A., Giménez-Capitán, A., Bertran-Alamillo, J., Karachaliou, N., Gervais, R., Massuti, B., Wei, J., Moran, T., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2233 · Cited by 229
Self-citationBoshuizen, J., Koopman, L. A., Krijgsman, O., Shahrabi, A., van den Heuvel, E. G., Ligtenberg, M. A., Vredevoogd, D. W., Kemper, K., Kuilman, T., Song, J.-Y., et al. (2018) · Nature Medicine · doi:10.1038/nm.4472 · Cited by 229
Murtuza, A., Bulbul, A., Shen, J. P., Keshavarzian, P., Woodward, B. D., Lopez-Diaz, F. J., Lippman, S. M., & Husain, H. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-1281 · Cited by 226
Mechanisms of Acquired Resistance to AZD9291
Kim, T. M., Song, A., Kim, D., Kim, S., Ahn, Y., Keam, B., Jeon, Y. K., Lee, S., Chung, D. H., & Heo, D. S. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000688 · Cited by 225
Self-citationPhenotype Switching: Tumor Cell Plasticity as a Resistance Mechanism and Target for Therapy
Kemper, K., de Goeje, P. L., Peeper, D. S., & van Amerongen, R. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1174 · Cited by 216
Mikubo, M., Inoue, Y., Liu, G., & Tsao, M. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.07.017 · Cited by 218
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities
Russo, M., Chen, M., Mariella, E., Peng, H., Rehman, S. K., Sancho, E., Sogari, A., Toh, T. S., Balaban, N. Q., Batlle, E., et al. (2024) · Nature Reviews Cancer · doi:10.1038/s41568-024-00737-z · Cited by 210
AXL Inhibitors in Cancer: A Medicinal Chemistry Perspective
Myers, S. H., Brunton, V. G., & Unciti‐Broceta, A. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01273 · Cited by 213
EMT: A mechanism for escape from EGFR-targeted therapy in lung cancer
Tulchinsky, E. M., Demidov, O. N., Kriajevska, M. V., Barlev, N. A., & Имянитов, Е. Н. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.10.003 · Cited by 214
Combined EGFR/MEK Inhibition Prevents the Emergence of Resistance in EGFR -Mutant Lung Cancer
Tricker, E. M., Xu, C., Uddin, S., Capelletti, M., Ercan, D., Ogino, A., Pratilas, C. A., Rosen, N. X., Gray, N. S., Wong, K., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0063 · Cited by 220
Blakely, C. M., Pazarentzos, E., Olivas, V., Asthana, S., Yan, J. J., Tan, I., Hrustanovic, G., Chan, E., Lin, L., Neel, D. S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.012 · Cited by 204
Self-citationTan, D. S. W., Yom, S. S., Tsao, M. S., Pass, H. I., Kelly, K., Peled, N., Yung, R. C., Wistuba, I. I., Yatabe, Y., Unger, M., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.05.008 · Cited by 201
Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer
de Bruin, E. C., Cowell, C., Warne, P. H., Jiang, M. Z., Saunders, R. E., Melnick, M. A., Gettinger, S. N., Walther, Z., Wurtz, A., Heynen, G. J. J. E., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0741 · Cited by 201
Self-citationAXL Mediates Resistance to Cetuximab Therapy
Brand, T. M., Iida, M., Stein, A. P., Corrigan, K. L., Braverman, C. M., Luthar, N., Toulany, M., Gill, P. S., Salgia, R., Kimple, R. J., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0294 · Cited by 198
Metadata
- Authors
- Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., Choi, Y. J., Choi, C.-M., Kim, S.-W., Jang, S. J., Park, Y. S., Kim, W. S., Lee, D. H., Lee, J.-S., Miller, V. A., Arcila, M., Ladanyi, M., Moonsamy, P., Sawyers, C., Boggon, T. J., Ma, P. C., Costa, C., Taron, M., Rosell, R., Halmos, B., & Bivona, T. G.
- Affiliations
- Columbia University Irving Medical Center (US)
- Asan Medical Center (KR)
- University of California, San Francisco (US)
- University Hospitals Cleveland Medical Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Yale University (US)
- Cleveland Clinic (US)
- Institut Català d'Oncologia (ES)
- Corresponding author
- Bivona, Trever G
- ORCID
- Zhang, Zhenfeng
- Lee, Jae Cheol
- Lin, Luping
- LaFramboise, Thomas
- Wang, Xiaoqi
- Levine, Alan D
- Rho, Jin Kyung
- Choi, Yun Jung
- Choi, Chang-Min
- Jang, Se Jin
- Park, Young Soo
- Kim, Woo Sung
- Lee, Dae Ho
- Lee, Jung-Shin
- Miller, Vincent A
- Arcila, Maria
- Ladanyi, Marc
- Moonsamy, Philicia
- Sawyers, Charles
- Boggon, Titus J
- Rosell, Rafael
- Bivona, Trever G
- Venue
- Nature Genetics
- Published
- 2012-07-01
- Volume
- 44
- Issue
- 8
- Pages
- 852-860
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3408577
- OpenAlex
- W1983774108
- Cited by
- 1,224
- References
- 29
- Citations by year
- 2026: 37 · 2025: 61 · 2024: 49 · 2023: 85 · 2022: 73 · 2021: 86 · 2020: 101 · 2019: 89 · 2018: 103 · 2017: 112 · 2016: 116 · 2015: 131 · 2014: 82 · 2013: 82 · 2012: 14
- FWCI
- 80.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T35HL007616)
- National Cancer Institute (R01CA169338, DP2CA174497, P01CA129243, K08CA154787, K08 1K08CA154787)
- 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
- AXL kinase, erlotinib resistance, EGFR-mutant lung cancer, non-small cell lung cancer, tyrosine kinase inhibitors, epithelial-mesenchymal transition, Gas6, acquired drug resistance, therapeutic target, MET kinase
- MeSH terms
- Erlotinib Hydrochloride, Axl Receptor Tyrosine Kinase, Growth Arrest-Specific Protein 6, Adult, Aged, Animals, Carcinoma, Non-Small-Cell Lung, Enzyme Activation, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Proto-Oncogene Proteins, Quinazolines, Signal Transduction, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Receptor Protein-Tyrosine Kinases, Xenograft Model Antitumor Assays, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Protein Kinase Inhibitors, Epithelial-Mesenchymal Transition, 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.
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
