Cited by 1,134Melanoma and MAPK PathwaysLung Cancer Treatments and MutationsCancer Mechanisms and Therapy

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Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors

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Wilson, Timothy R., Fridlyand, Jane, Yan, Yibing, Penuel, Elicia, Burton, Luciana, Chan, Emily, Peng, Jing, Lin, Eva, Wang, Yulei, Sosman, Jeff, Ribas, Antoni, Li, Jiang, Moffat, John, Sutherlin, Daniel P., Koeppen, Hartmut, Merchant, Mark, Neve, Richard, Settleman, Jeff·2012·Nature

DOI 10.1038/nature11249PMC PMC3724525

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Abstract

Mutationally activated kinases define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumours harbour such alleles is invariably limited by innate or acquired drug resistance. The identification of resistance mechanisms has revealed a recurrent theme—the engagement of survival signals redundant to those transduced by the targeted kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell-survival effectors—most notably, phosphatidylinositol-3-OH kinase (PI(3)K) and mitogen-activated protein kinase (MAPK). Consequently, an increase in RTK-ligand levels, through autocrine tumour-cell production, paracrine contribution from tumour stroma or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signalling output. Here, using a panel of kinase-'addicted' human cancer cell lines, we found that most cells can be rescued from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical implications was the observation that hepatocyte growth factor (HGF) confers resistance to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF-mutant melanoma cells. These observations highlight the extensive redundancy of RTK-transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.

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Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720
MET 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
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Kwak, E. L., Bang, Y., Camidge, D. R., Shaw, A. T., Solomon, B., Maki, R. G., Ou, S. I., Dezube, B. J., Janne, P. A., Costa, D. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1006448 · Cited by 4,477
Genotypic 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
A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaran, S., McDermott, U., Azizian, N., Zou, L., Fischbach, M. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.02.027 · Cited by 2,770
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M., Attar, N., Sazegar, H., et al. (2010) · Nature · doi:10.1038/nature09626 · Cited by 2,244
Friends or foes — bipolar effects of the tumour stroma in cancer
Mueller, M. M., & Fusenig, N. E. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1477 · Cited by 1,817
Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion
Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z. R., Du, J., Davis, A., Mongare, M. M., Gould, J., Frederick, D. T., et al. (2012) · Nature · doi:10.1038/nature11183 · Cited by 1,771
Self-citation
COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460
Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC
Turke, A. B., Zejnullahu, K., Wu, Y.-L., Song, Y., Dias-Santagata, D., Lifshits, E., Toschi, L., Rogers, A., Mok, T., Sequist, L., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.11.022 · Cited by 1,059

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Arandkar, S., Furth, N., Elisha, Y., Nataraj, N. B., van der Kuip, H., Yarden, Y., Aulitzky, W. E., Ulitsky, I., Geiger, B., & Oren, M. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1719076115 · Cited by 115
Determinants and functions of CAFs secretome during cancer progression and therapy
Linares, J., Marín-Jiménez, J. A., Badia-Ramentol, J., & Calon, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.621070 · Cited by 110
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Gerosa, L., Chidley, C., Fröhlich, F., Sanchez, G., Lim, S. K., Muhlich, J. L., Chen, J.-Y., Vallabhaneni, S., Baker, G. J., Schapiro, D., et al. (2020) · Cell Systems · doi:10.1016/j.cels.2020.10.002 · Cited by 111
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Winder, M. L., & Virós, A. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_17 · Cited by 112
Unbiased Combinatorial Screening Identifies a Bispecific IgG1 that Potently Inhibits HER3 Signaling via HER2-Guided Ligand Blockade
Geuijen, C. A. W., Nardis, C. D., Maussang, D., Rovers, E., Gallenne, T., Hendriks, L. J. A., Visser, T., Nijhuis, R., Logtenberg, T., de Kruif, J., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.04.003 · Cited by 108
Rescue Screens with Secreted Proteins Reveal Compensatory Potential of Receptor Tyrosine Kinases in Driving Cancer Growth
Harbinski, F., Craig, V. J., Sanghavi, S., Jeffery, D. A., Liu, L., Sheppard, K. A., Wagner, S., Stamm, C., Buneß, A., Chatenay‐Rivauday, C., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0237 · Cited by 107
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Yoshida, T., Zhang, G., Smith, M. A., Lopez, A. S., Bai, Y., Li, J., Fang, B., Koomen, J. M., Rawal, B., Fisher, K. J., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1559 · Cited by 106
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Li, F., Huynh, H. T., Li, X., Ruddy, D. A., Wang, Y., Ong, R., Chow, P. K. H., Qiu, S., Tam, A., Rakiec, D. P., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0763 · Cited by 108
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Multitask learning improves prediction of cancer drug sensitivity
Yuan, H., Paskov, I., Paskov, H. S., González, A. J., & Leslie, C. S. (2016) · Scientific Reports · doi:10.1038/srep31619 · Cited by 104
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Shien, K., Papadimitrakopoulou, V. A., Ruder, D., Behrens, C., Shen, L., Kalhor, N., Song, J., Lee, J. J., Wang, J., Tang, X., et al. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0148 · Cited by 109
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Vultur, A., Villanueva, J., Krepler, C., Rajan, G., Chen, Q., Xiao, M., Li, L., Gimotty, P. A., Wilson, M. A., Hayden, J., et al. (2013) · Oncogene · doi:10.1038/onc.2013.131 · Cited by 101
Treatment of Triple-Negative Breast Cancer with TORC1/2 Inhibitors Sustains a Drug-Resistant and Notch-Dependent Cancer Stem Cell Population
Bhola, N. E., Jansen, V. M., Koch, J. P., Li, H., Formisano, L., Williams, J. A., Grandis, J. R., & Arteaga, C. L. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-1640-t · Cited by 103
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Sun, Y. (2015) · Medicinal Research Reviews · doi:10.1002/med.21338 · Cited by 85
Ipilimumab, Vemurafenib, Dabrafenib, and Trametinib: Synergistic Competitors in the Clinical Management of BRAF Mutant Malignant Melanoma
Luke, J. J., & Hodi, F. S. (2013) · The Oncologist · doi:10.1634/theoncologist.2012-0391 · Cited by 84
Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated Drug Resistance via Balanced Inhibition of MET, TIE2, and VEGFR2
Smith, B. D., Kaufman, M. D., Leary, C. B., Turner, B. A., Wise, S., Ahn, Y. M., Booth, R. J., Caldwell, T. M., Ensinger, C. L., Hood, M. M., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-1105 · Cited by 82
Emerging Roles of SIRT1 in Cancer Drug Resistance
Wang, Z., & Chen, W. (2013) · Genes & Cancer · doi:10.1177/1947601912473826 · Cited by 87
Cisplatin-induced mesenchymal stromal cells-mediated mechanism contributing to decreased antitumor effect in breast cancer cells
Miklikova, S., Matúšková, M., Boháč, M., Toro, L., Durinikova, E., Tyčiaková, S., Demková, L., Gurský, J., & Kučerová, L. (2016) · Cell Communication and Signaling · doi:10.1186/s12964-016-0127-0 · Cited by 82
miR-147b-mediated TCA cycle dysfunction and pseudohypoxia initiate drug tolerance to EGFR inhibitors in lung adenocarcinoma
Zhang, W. C., Wells, J. M., Chow, K.-H., Huang, H., Yuan, M., Saxena, T., Melnick, M. A., Politi, K. A., Asara, J. M., Costa, D. B., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0052-9 · Cited by 84
Control of NF ‐ kB activity in human melanoma by bromodomain and extra‐terminal protein inhibitor I ‐ BET 151
Gallagher, S. J., Mijatov, B., Gunatilake, D., Gowrishankar, K., Tiffen, J. C., James, W. F., Jin, L., Pupo, G. M., Cullinane, C. M., McArthur, G. A., et al. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12282 · Cited by 82
Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D Culture into Hepatocyte-like Cells through Direct Wnt/β-catenin Pathway Inhibition
Pettinato, G., Ramanathan, R., Fisher, R. A., Mangino, M. J., Zhang, N., & Wen, X. (2016) · Scientific Reports · doi:10.1038/srep32888 · Cited by 81
Mixed lineage kinases activate MEK independently of RAF to mediate resistance to RAF inhibitors
Marusiak, A. A., Edwards, Z. C., Hugo, W., Trotter, E. W., Girotti, M. R., Stephenson, N. L., Kong, X., Gartside, M. G., Fawdar, S., Hudson, A., et al. (2014) · Nature Communications · doi:10.1038/ncomms4901 · Cited by 86
PPAR-delta promotes survival of breast cancer cells in harsh metabolic conditions
Wang, X., Wang, G., Shi, Y., Sun, L., Gorczynski, R. M., Li, Y., Xu, Z., & Spaner, D. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.41 · Cited by 82
The role of microenvironment and immunity in drug response in leukemia
Bakker, E. Y., Qattan, M. Y., Mutti, L., Demonacos, C., & Krstic–Demonacos, M. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.08.003 · Cited by 83
Organoid screening reveals epigenetic vulnerabilities in human colorectal cancer
Toshimitsu, K., Takano, A., Fujii, M., Togasaki, K., Matano, M., Takahashi, S., Kanai∥, T., & Sato, T. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-00984-x · Cited by 84
Neuropilin-1 upregulation elicits adaptive resistance to oncogene-targeted therapies
Rizzolio, S., Cagnoni, G., Battistini, C., Bonelli, S., Isella, C., Ginderachter, J. A. V., Bernards, R., Nicolantonio, F. D., Giordano, S., & Tamagnone, L. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99257 · Cited by 78
EGFR Mediates Responses to Small-Molecule Drugs Targeting Oncogenic Fusion Kinases
Vaishnavi, A., Schubert, L., Rix, U., Marek, L. A., Le, A. T., Keysar, S. B., Glogowska, M. J., Smith, M. A., Kako, S. L., Sumi, N. J., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0109 · Cited by 76
Transmembrane protein CD9 is glioblastoma biomarker, relevant for maintenance of glioblastoma stem cells
Podergajs, N., Motaln, H., Rajčević, U., Verbovšek, U., Koršič, M., Obad, N., Espedal, H., Vittori, M., Herold-Mende, C., Miletic, H., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.5477 · Cited by 81
B-Raf Inhibition in the Clinic: Present and Future
Fiskus, W. C., & Mitsiades, N. (2016) · Annual Review of Medicine · doi:10.1146/annurev-med-090514-030732 · Cited by 79
Cancer-associated fibroblast-induced lncRNA UPK1A-AS1 confers platinum resistance in pancreatic cancer via efficient double-strand break repair
Zhang, X., Zheng, S., Hu, C., Li, G., Lin, H., Xia, R., Ye, Y., He, R., Li, Z., Lin, Q., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02253-6 · Cited by 80
IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells
Rix, L. L. R., Sumi, N. J., Hu, Q., Desai, B., Bryant, A. T., Li, X., Welsh, E. A., Fang, B., Kinose, F., Kuenzi, B. M., et al. (2022) · Science Signaling · doi:10.1126/scisignal.abj5879 · Cited by 76
Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism
Zhang, Q., Liu, J., Liu, B., Xia, J., Chen, N., Chen, X., Cao, Y., Zhang, C., Lu, C., Li, M., et al. (2014) · Scientific Reports · doi:10.1038/srep04628 · Cited by 78
CTGF is a therapeutic target for metastatic melanoma
Finger, E. C., Cheng, C.-F., Williams, T. R., Rankin, E. B., Bedogni, B., Tachiki, L. M. L., Spong, S. M., Giaccia, A. J., & Powell, M. B. (2013) · Oncogene · doi:10.1038/onc.2013.47 · Cited by 77
MEK1 is associated with carboplatin resistance and is a prognostic biomarker in epithelial ovarian cancer
Pénzváltó, Z., Lánczky, A., Lénárt, J., Meggyesházi, N., Krenács, T., Szoboszlai, N., Denkert, C., Pete, I., & Győrffy, B. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-837 · Cited by 81
Implications of BRAF V600E mutation in gliomas: Molecular considerations, prognostic value and treatment evolution
Nunno, V. D., Gatto, L., Tosoni, A., Bartolini, S., & Franceschi, E. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1067252 · Cited by 79
Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation
Kim, H., Frederick, D. T., Levesque, M. P., Cooper, Z. A., Feng, Y., Krepler, C., Brill, L. M., Samuels, Y., Hayward, N. K., Perlina, A., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.049 · Cited by 77
Inflammation-Induced Plasticity in Melanoma Therapy and Metastasis
Hölzel, M., & Tüting, T. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.03.009 · Cited by 80
Targeting MET and EGFR crosstalk signaling in triple-negative breast cancers
Linklater, E. S., Tovar, E. A., Essenburg, C. J., Turner, L., Madaj, Z., Winn, M. E., Melnik, M. K., Körkaya, H., Maroun, C. R., Christensen, J. G., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.12065 · Cited by 77
Resistance to RAF Inhibitors Revisited
Hartsough, E. J., Shao, Y., & Aplin, A. E. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.358 · Cited by 82
Mechanisms of Resistance to PARP Inhibitors—Three and Counting
Fojo, T., & Bates, S. E. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0514 · Cited by 79
Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS -Mutant Lung Cancer
Kim, J., Welsh, E. A., Fang, B., Bai, Y., Kinose, F., Eschrich, S. A., Koomen, J. M., & Haura, E. B. (2016) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0506 · Cited by 76
Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface
Claus, J., Patel, G. S., Autore, F., Colomba, A., Weitsman, G. E., Soliman, T. N., Roberts, S. K., Zanetti-Domingues, L. C., Hirsch, M., Collu, F., et al. (2018) · eLife · doi:10.7554/elife.32271 · Cited by 74
Roles of tumor heterogeneity in the development of drug resistance: A call for precision therapy
Wu, D., Wang, D. C., Cheng, Y., Qian, M., Zhang, M., Shen, Q., & Wang, X. (2016) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2016.11.006 · Cited by 77
Cancer drug resistance: A fleet to conquer
Hussain, S., Singh, A., Nazir, S. U., Tulsyan, S., Khan, A., Kumar, R., Bashir, N., Tanwar, P., & Mehrotra, R. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28782 · Cited by 80
Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors
Whittaker, S. R., Cowley, G. S., Wagner, S., Luo, F., Root, D. E., & Garraway, L. A. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0136-t · Cited by 75

Authors: Wilson, T. R., Fridlyand, J., Yan, Y., Penuel, E., Burton, L., Chan, E., Peng, J., Lin, E., Wang, Y., Sosman, J., Ribas, A., Li, J., Moffat, J., Sutherlin, D. P., Koeppen, H., Merchant, M., Neve, R., & Settleman, J.
Affiliations: Genentech (US)
Vanderbilt University Medical Center (US)
University of California, Los Angeles (US)
Corresponding author: Settleman, Jeff
ORCID: Wilson, Timothy R.
Penuel, Elicia
Chan, Emily
Peng, Jing
Lin, Eva
Wang, Yulei
Ribas, Antoni
Koeppen, Hartmut
Merchant, Mark
Neve, Richard
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2012-07
Volume: 487
Issue: 7408
Pages: 505-509
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature11249
PMC: PMC3724525
OpenAlex: W1999025555
Cited by: 1,134
References: 29
Citations by year: 2026: 23 · 2025: 16 · 2024: 31 · 2023: 46 · 2022: 47 · 2021: 51 · 2020: 65 · 2019: 70 · 2018: 85 · 2017: 87 · 2016: 125 · 2015: 137 · 2014: 166 · 2013: 150 · 2012: 34
FWCI: 62.91
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Cancer Institute (K24CA097588)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
Keywords: drug resistance, kinase inhibitors, receptor tyrosine kinase, growth factors, hepatocyte growth factor, BRAF inhibitors, vemurafenib, melanoma, tumor microenvironment, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, combination therapy
MeSH terms: Lapatinib, Vemurafenib, Antineoplastic Agents, Breast Neoplasms, Cell Survival, Female, Humans, Indoles, Ligands, Melanoma, Quinazolines, Sulfonamides, Signal Transduction, Hepatocyte Growth Factor, Erb-b2 Receptor Tyrosine Kinases, Receptor, ErbB-2, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, Receptor Protein-Tyrosine Kinases, Mitogen-Activated Protein Kinases, Cell Line, Tumor, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf

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Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors

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