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

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

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

Open access

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

Open this paper in CoChat — free account

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.

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

Crossref · 10.1038/nature11249

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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

Flagged first, then by citations

Show all 29 references

Sorted by citations

Items 301–400 of 1,000

Emerging insights into resistance to BRAF inhibitors in melanoma
Bucheit, A. D., & Davies, M. A. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.11.013 · Cited by 77
Genetic Alterations and Personalized Medicine in Melanoma: Progress and Future Prospects
Griewank, K., Scolyer, R. A., Thompson, J. F., Flaherty, K. T., Schadendorf, D., & Murali, R. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt435 · Cited by 77
Fibroblast Growth Factor Receptor Signaling in Skin Cancers
Czyż, M. (2019) · Cells · doi:10.3390/cells8060540 · Cited by 74
HGF/c-MET Axis in Tumor Microenvironment and Metastasis Formation
Spina, A., Pasquale, V. D., Cerulo, G., Cocchiaro, P., Morte, R. D., Avallone, L., & Pavone, L. M. (2015) · Biomedicines · doi:10.3390/biomedicines3010071 · Cited by 75
Diminished WNT → β-catenin → c-MYC signaling is a barrier for malignant progression of BRAFV600E-induced lung tumorsPreprint
Juan, J. M., Muraguchi, T., Iezza, G., Sears, R. C., & McMahon, M. (2014) · Genes & Development · doi:10.1101/gad.233627.113 · Cited by 73
Failure to Induce Apoptosis via BCL-2 Family Proteins Underlies Lack of Efficacy of Combined MEK and PI3K Inhibitors for KRAS-Mutant Lung Cancers
Hata, A. N., Yeo, A., Faber, A. C., Lifshits, E., Chen, Z., Cheng, K. A., Walton, Z., Sarosiek, K. A., Letai, A., Heist, R. S., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3728 · Cited by 74
Engineering in Medicine To Address the Challenge of Cancer Drug Resistance: From Micro- and Nanotechnologies to Computational and Mathematical Modeling
Craig, M., Jenner, A. L., Namgung, B., Lee, L. P., & Goldman, A. J. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00356 · Cited by 74
The importance of being CAFs (in cancer resistance to targeted therapies)
Rizzolio, S., Giordano, S., & Corso, S. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02524-w · Cited by 75
The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study
Bunney, T. D., Wan, S., Thiyagarajan, N., Sutto, L., Williams, S. V., Ashford, P., Koss, H., Knowles, M. A., Gervasio, F. L., Coveney, P. V., et al. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.02.009 · Cited by 76
Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors
Sambrooks, C. L., Baro, M., Quijano, A., Narayan, A., Cui, W., Greninger, P., Egan, R. K., Patel, A. A., Benes, C. H., Saltzman, W. M., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0505 · Cited by 74
Oncogene Mimicry as a Mechanism of Primary Resistance to BRAF Inhibitors
Sos, M. L., Levin, R. S., Gordan, J. D., Osés-Prieto, J. A., Webber, J. T., Salt, M. B., Hann, B. C., Burlingame, A. L., McCormick, F. P., Bandyopadhyay, S., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.010 · Cited by 72
JUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma
Titz, B., Lomova, A., Le, A., Hugo, W., Kong, X., ten Hoeve, J., Friedman, M., Shi, H., Moriceau, G., Song, C., et al. (2016) · Cell Discovery · doi:10.1038/celldisc.2016.28 · Cited by 75
Influence of Tumor Microenvironment and Fibroblast Population Plasticity on Melanoma Growth, Therapy Resistance and Immunoescape
Romano, V., Belviso, I., Venuta, A., Ruocco, M. R., Masone, S., Aliotta, F., Fiume, G., Montagnani, S., Avagliano, A., & Arcucci, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105283 · Cited by 78
Therapeutically targeting tumor microenvironment–mediated drug resistance in estrogen receptor–positive breast cancer
Shee, K., Yang, W., Hinds, J. W., Hampsch, R. A., Varn, F. S., Traphagen, N. A., Patel, K., Cheng, C., Jenkins, N. P., Kettenbach, A. N., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171818 · Cited by 75
Preclinical evaluation of dasatinib alone and in combination with cabozantinib for the treatment of diffuse intrinsic pontine glioma
Truffaux, N., Philippe, C., Paulsson, J., Andreiuolo, F. D. M., Guerrini‐Rousseau, L., Cornilleau, G., Dret, L. L., Richon, C., Lacroix, L., Puget, S., et al. (2014) · Neuro-Oncology · doi:10.1093/neuonc/nou330 · Cited by 76
Ferroptosis and Tumor Drug Resistance: Current Status and Major Challenges
Nie, Z., Chen, M., Gao, Y., Huang, D., Cao, H., Peng, Y., Guo, N., Wang, F., & Zhang, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.879317 · Cited by 83
Ligand-associated ERBB2/3 activation confers acquired resistance to FGFR inhibition in FGFR3-dependent cancer cells
Wang, J., Mikse, O. R., Liao, R. G., Li, Y. Y., Tan, L., Janne, P. A., Gray, N. S., Wong, K., & Hammerman, P. S. (2014) · Oncogene · doi:10.1038/onc.2014.161 · Cited by 70
MET/HGF pathway activation as a paradigm of resistance to targeted therapies
Ko, B., He, T., Gadgeel, S. M., & Halmos, B. (2017) · Annals of Translational Medicine · doi:10.21037/atm.2016.12.09 · Cited by 71
TPP-based mitocans: a potent strategy for anticancer drug design
Wang, J., Li, J., Xiao, Y., Fu, B., & Qin, Z. (2020) · RSC Medicinal Chemistry · doi:10.1039/c9md00572b · Cited by 72
Thirty Years of Research on Met Receptor to Move a Biomarker from Bench to Bedside
Furlan, A., Kherrouche, Z., Montagne, R., Copin, M., & Tulasne, D. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1932 · Cited by 70
Combinatorial targeting of FGF and ErbB receptors blocks growth and metastatic spread of breast cancer models
Issa, A., Gill, J. W., Heideman, M. R., Şahin, Ö., Wiemann, S., Dey, J. H., & Hynes, N. E. (2013) · Breast Cancer Research · doi:10.1186/bcr3379 · Cited by 73
Fibroblast-derived Neuregulin 1 Promotes Compensatory ErbB3 Receptor Signaling in Mutant BRAF Melanoma
Capparelli, C., Rosenbaum, S. R., Berger, A. C., & Aplin, A. E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.657270 · Cited by 67
CD95 in cancer: tool or target?
Martín-Villalba, A., Llorens-Bobadilla, E., & Wollny, D. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.03.002 · Cited by 70
Heterogeneity in Melanoma
Shannan, B., Perego, M., Somasundaram, R., & Herlyn, M. (2015) · Cancer treatment and research · doi:10.1007/978-3-319-22539-5_1 · Cited by 70
Intercellular Resistance to BRAF Inhibition Can Be Mediated by Extracellular Vesicle–Associated PDGFRβ
Vella, L. J., Behren, A., Coleman, B. M., Greening, D. W., Hill, A. F., & Cebon, J. S. (2017) · Neoplasia · doi:10.1016/j.neo.2017.07.002 · Cited by 70
Gold Nanoparticle Transforms Activated Cancer-Associated Fibroblasts to Quiescence
Hossen, M. N., Rao, G., Dey, A., Robertson, J. D., Bhattacharya, R., & Mukherjee, P. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b03313 · Cited by 70
Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies
Montero, J., Gstalder, C., Kim, D. J., Sadowicz, D. E., Miles, W. O., Manos, M. P., Cidado, J. R., Secrist, J. P., Tron, A. E., Flaherty, K. T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12477-y · Cited by 71
BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity
Cabanillas, M. E., Patel, A. P., Danysh, B. P., Dadu, R., Kopetz, S., & Falchook, G. S. (2014) · Hormones and Cancer · doi:10.1007/s12672-014-0207-9 · Cited by 69
Cancer systems biology in the genome sequencing era: Part 2, evolutionary dynamics of tumor clonal networks and drug resistance
Wang, E., Zou, J., Zaman, N., Beitel, L. K., Trifiro, M. A., & Paliouras, M. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.06.001 · Cited by 70
Dual inhibition of Akt and c‐Met as a second‐line therapy following acquired resistance to sorafenib in hepatocellular carcinoma cells
Han, P., Li, H., Jiang, X. L., Zhai, B., Tan, G., Zhao, D., Qiao, H., Liu, B., Jiang, H., & Sun, X. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12039 · Cited by 70
FGF2-FGFR1 signaling regulates release of Leukemia-Protective exosomes from bone marrow stromal cells
Javidi‐Sharifi, N., Martinez, J., English, I. A., Joshi, S. K., Scopim‐Ribeiro, R., Viola, S. K., Edwards, D. K., V, Agarwal, A., López, C. S., Jorgens, D. M., et al. (2019) · eLife · doi:10.7554/elife.40033 · Cited by 69
Role of targeted agents in metastatic colorectal cancer
Prenen, H., Vecchione, L., & Cutsem, E. V. (2013) · Targeted Oncology · doi:10.1007/s11523-013-0281-x · Cited by 70
PI3K/mTOR pathway inhibitors sensitize chronic myeloid leukemia stem cells to nilotinib and restore the response of progenitors to nilotinib in the presence of stem cell factor
Airiau, K., Mahon, F., Josselin, M., Jeanneteau, M., & Belloc, F. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.309 · Cited by 73
AEBP1 upregulation confers acquired resistance to BRAF (V600E) inhibition in melanoma
Hu, W., Jin, L., Jiang, C. C., Long, G. V., Scolyer, R. A., Wu, Q., Zhang, X. D., Mei, Y., & Wu, M. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.441 · Cited by 72
Functional Genetic Approach Identifies MET, HER3, IGF1R, INSR Pathways as Determinants of Lapatinib Unresponsiveness in HER2-Positive Gastric Cancer
Zhang, Z., Wang, J., Ji, D., Wang, C., Liu, R., Wu, Z., Liu, L., Zhu, D., Chang, J., Geng, R., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3396 · Cited by 69
Cancer plasticity in therapy resistance: Mechanisms and novel strategies
Niu, X., Liu, W., Yinling, Z., Liu, J., Zhang, J., Li, B., Qiu, Y., Zhao, P., Wang, Z., & Wang, Z. (2024) · Drug Resistance Updates · doi:10.1016/j.drup.2024.101114 · Cited by 68
Prognostic Significance in Breast Cancer of a Gene Signature Capturing Stromal PDGF Signaling
Frings, O., Augsten, M., Tobin, N. P., Carlson, J. W., Paulsson, J., Peña, C., Olsson, E., Veerla, S., Bergh, J. C. S., Östman, A., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.02.018 · Cited by 67
Receptor Tyrosine Kinases Fall into Distinct Classes Based on Their Inferred Signaling Networks
Wagner, J. P., Wolf‐Yadlin, A., Sevecka, M., Grenier, J. K., Root, D. E., Lauffenburger, D. A., & MacBeath, G. (2013) · Science Signaling · doi:10.1126/scisignal.2003994 · Cited by 68
Mechanisms of resistance to EGFR targeted therapies
Hrustanovic, G., Lee, B. J., & Bivona, T. G. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.23627 · Cited by 67
Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis
Phillips, G. D. L., Nishimura, M. C., Lacap, J. A., Kharbanda, S., Mai, E., Tien, J., Malesky, K., Williams, S. P., Mařı́k, J., & PHILLIPS, H. S. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4279-4 · Cited by 66
A nanoparticle formulation that selectively transfects metastatic tumors in mice
Yang, J., Hendricks, W. P. D., Liu, G., McCaffery, J. M., Kinzler, K. W., Huso, D. L., Vogelstein, B., & Zhou, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313330110 · Cited by 64
Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer
You, K. S., Yi, Y. W., Cho, J., Park, J., & Seong, Y. (2021) · Pharmaceuticals · doi:10.3390/ph14060589 · Cited by 64
A critical role for HER3 in HER2-amplified and non-amplified breast cancers: function of a kinase-dead RTK.
Dey, N., Williams, C. B., Leyland-Jones, B., & De, P. K. (2015) · PubMed · Cited by 64
Current perspectives of cancer-associated fibroblast in therapeutic resistance: potential mechanism and future strategy
Kadel, D., Zhang, Y., Sun, H., Zhao, Y., Dong, Q., & Qin, L. (2019) · Cell Biology and Toxicology · doi:10.1007/s10565-019-09461-z · Cited by 62
Current State of Melanoma Therapy and Next Steps: Battling Therapeutic Resistance
Fateeva, A., Eddy, K., & Chen, S. (2024) · Cancers · doi:10.3390/cancers16081571 · Cited by 67
Pushing tumor cells towards a malignant phenotype: Stimuli from the microenvironment, intercellular communications and alternative roads
Marcucci, F., Bellone, M., Caserta, C. A., & Corti, A. (2013) · International Journal of Cancer · doi:10.1002/ijc.28572 · Cited by 64
Overcoming acquired resistance to cetuximab by dual targeting HER family receptors with antibody-based therapy
Iida, M., Brand, T. M., Starr, M. M., Huppert, E. J., Luthar, N., Bahrar, H., Coan, J. P., Pearson, H. E., Salgia, R., & Wheeler, D. L. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-242 · Cited by 63
PTEN Loss-of-Function Alterations Are Associated With Intrinsic Resistance to BRAF Inhibitors in Metastatic Melanoma
Catalanotti, F., Cheng, D. T., Shoushtari, A. N., Johnson, D. B., Panageas, K. S., Momtaz, P., Higham, C., Won, H. H., Harding, J. J., Merghoub, T., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.16.00054 · Cited by 70
Pharmaceutical properties of supramolecular assembly of co-loaded cardanol/triazole-halloysite systems
Massaro, M., Colletti, C. G., Noto, R., Riela, S., Poma, P., Guernelli, S., Parisi, F., Milioto, S., & Lazzara, G. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.12.004 · Cited by 62
Nanoplatform-based natural products co-delivery system to surmount cancer multidrug-resistant
Liang, Y., Liu, Z.-Y., Wang, P., Li, Y., Wang, R., & Xie, S. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.06.034 · Cited by 63
Changes in the Secretory Profile of NSCLC-Associated Fibroblasts after Ablative Radiotherapy: Potential Impact on Angiogenesis and Tumor Growth
Hellevik, T., Pettersen, I., Berg, V., Bruun, J., Bartnes, K., Busund, L., Chalmers, A. J., Bremnes, R. M., & Martínez-Zubiaurre, I. (2013) · Translational Oncology · doi:10.1593/tlo.12349 · Cited by 62
Genetic modifiers of the BRD4-NUT dependency of NUT midline carcinoma uncovers a synergism between BETis and CDK4/6isPreprint
Liao, S., Maertens, O., Cichowski, K. M., & Elledge, S. J. (2018) · Genes & Development · doi:10.1101/gad.315648.118 · Cited by 64
The Intersection of Immune-Directed and Molecularly Targeted Therapy in Advanced Melanoma: Where We Have Been, Are, and Will Be
Sullivan, R. J., LoRusso, P. M., & Flaherty, K. T. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2151 · Cited by 63
Mechanisms of resistance to BCR-ABL and other kinase inhibitors
Lamontanara, A. J., Akçok, E. B. G., Kuzyk, O., & Hantschel, O. D. (2012) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2012.12.009 · Cited by 65
Inactivation of ABL kinases suppresses non–small cell lung cancer metastasis
Gu, J., Rouse, C., Xu, X., Wang, J., Onaitis, M. W., & Pendergast, A. M. (2016) · JCI Insight · doi:10.1172/jci.insight.89647 · Cited by 63
Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cells
Misek, S. A., Appleton, K. M., Dexheimer, T. S., Lisabeth, E. M., Lo, R. S., Larsen, S. D., Gallo, K. A., & Neubig, R. R. (2019) · Oncogene · doi:10.1038/s41388-019-1074-1 · Cited by 64
Effective inhibition of c-MET-mediated signaling, growth and migration of ovarian cancer cells is influenced by the ovarian tissue microenvironment
Kwon, Y., Smith, B. D., Zhou, Y., Kaufman, M. D., & Godwin, A. K. (2013) · Oncogene · doi:10.1038/onc.2013.539 · Cited by 60
Anti-HDGF Targets Cancer and Cancer Stromal Stem Cells Resistant to Chemotherapy
Zhao, J., Ma, M. Z., Ren, H., Liu, Z., Edelman, M. J., Pan, H., & Mao, L. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3478 · Cited by 59
Metabolomics of the Tumor Microenvironment in Pediatric Acute Lymphoblastic Leukemia
Tiziani, S., Kang, Y., Harjanto, R., Axelrod, J. L., Piermarocchi, C., Roberts, W. D., & Paternostro, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082859 · Cited by 60
A Place for Precision Medicine in Bladder Cancer: Targeting the Fgfrs
di Martino, E., Tomlinson, D. C., Williams, S. V., & Knowles, M. A. (2016) · Future Oncology · doi:10.2217/fon-2016-0042 · Cited by 60
Targeting growth hormone receptor in human melanoma cells attenuates tumor progression and epithelial mesenchymal transition via suppression of multiple oncogenic pathways
Basu, R., Wu, S., & Kopchick, J. J. (2017) · Oncotarget · doi:10.18632/oncotarget.15375 · Cited by 61
Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibitionPreprint
Webster, D. E., Barajas, B. C., Bussat, R. T., Yan, K., Neela, P. H., Flockhart, R. J., Kovalski, J. R., Zehnder, A. M., & Khavari, P. A. (2014) · Genome Research · doi:10.1101/gr.166231.113 · Cited by 60
Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer
Ianza, A., Sirico, M., Bernocchi, O., & Generali, D. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.641449 · Cited by 62
Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis
Fernández‐Nogueira, P., Fuster, G., Gutiérrez-Uzquiza, Á., Gascón, P., Carbó, N., & Bragado, P. (2021) · Cancers · doi:10.3390/cancers13133146 · Cited by 59
MET Signaling Mediates Intestinal Crypt-Villus Development, Regeneration, and Adenoma Formation and Is Promoted by Stem Cell CD44 Isoforms
Joosten, S. P. J., Zeilstra, J., van Andel, H., Mijnals, R. C. D., Zaunbrecher, J., Duivenvoorden, A. A. M., van de Wetering, M., Clevers, H. C., Spaargaren, M., & Pals, S. T. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.07.008 · Cited by 58
The Evolution of Melanoma Resistance Reveals Therapeutic Opportunities
Thakur, M. D., & Stuart, D. D. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1633 · Cited by 59
A comprehensive review of 3D cancer models for drug screening and translational research
Sharma, K., Dey, S., Karmakar, R., & Rengan, A. K. (2023) · Cancer Innovation · doi:10.1002/cai2.102 · Cited by 60
Loss of USP28-mediated BRAF degradation drives resistance to RAF cancer therapies
Saei, A., Palafox, M., Benoukraf, T., Kumari, N., Jaynes, P. W., Iyengar, P. V., Muñoz‐Couselo, E., Nuciforo, P. G., Cortés, J., Nötzel, C., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171960 · Cited by 58
Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment
Manzella, L., Massimino, M., Stella, S., Tirrò, E., Pennisi, M. S., Martorana, F., Motta, G., Vitale, S. R., Puma, A., Romano, C., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133258 · Cited by 60
Molecular Pathways: Response and Resistance to BRAF and MEK Inhibitors in BRAFV600E Tumors
Thakur, M. D., & Stuart, D. D. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0103 · Cited by 57
Blood‐Lymphatic Integrated System with Heterogeneous Melanoma Spheroids via In‐Bath Three‐Dimensional Bioprinting for Modelling of Combinational Targeted Therapy
Cho, W., Ahn, M., Kim, B. S., & Cho, D. (2022) · Advanced Science · doi:10.1002/advs.202202093 · Cited by 56
Identification of PLX 4032‐resistance mechanisms and implications for novel RAF inhibitors
Choi, J., Landrette, S. F., Wang, T. L., Evans, P., Bacchiocchi, A., Bjornson, R. D., Cheng, E., Stiegler, A. L., Gathiaka, S. M., Acevedo, O., et al. (2013) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12197 · Cited by 58
Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis
Kang, X.-H., Xu, Z.-Y., Gong, Y.-B., Wang, L., Wang, Z., Xu, L., Cao, F., & Liao, M.-J. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/243859 · Cited by 58
A Randomized Phase 2 Study Comparing the Combination of Ficlatuzumab and Gefitinib with Gefitinib Alone in Asian Patients with Advanced Stage Pulmonary Adenocarcinoma
Mok, T. S. K., Geater, S. L., Su, W., Tan, E.-H., Yang, J. C., Chang, G., Han, M., Komarnitsky, P. B., Payumo, F. C., Garrus, J. E., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.05.038 · Cited by 57
Structural basis for the activation of PLC-gamma isozymes by phosphorylation and cancer-associated mutations
Hajicek, N., & Sondek, J. (2019) · Worldwide Protein Data Bank · doi:10.2210/pdb6pbc/pdb · Cited by 58
Update on the Targeted Therapy of Melanoma
Johnson, D. B., & Sosman, J. A. (2013) · Current Treatment Options in Oncology · doi:10.1007/s11864-013-0226-8 · Cited by 56
Overcoming resistance to targeted therapy with immunotherapy and combination therapy for metastatic melanoma
Keller, H. R., Zhang, X., Li, L., Schaider, H., & Wells, J. W. (2017) · Oncotarget · doi:10.18632/oncotarget.18523 · Cited by 55
Co-targeting cancer drug escape pathways confers clinical advantage for multi-target anticancer drugs
Tao, L., Zhu, F., Xu, F., Chen, Z., Jiang, Y., & Chen, Y. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.09.019 · Cited by 56
Enhanced MET Translation and Signaling Sustains K-Ras–Driven Proliferation under Anchorage-Independent Growth Conditions
Fujita-Sato, S., Galeas, J., Truitt, M., Pitt, C., Urisman, A., Bandyopadhyay, S., Ruggero, D., & McCormick, F. P. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-1623 · Cited by 56
Amphiregulin Is a Critical Downstream Effector of Estrogen Signaling in ERα-Positive Breast Cancer
Peterson, E. A., Jenkins, E. C., Lofgren, K. A., Emmanuel, N., Liu, H., Aranda, E., Barnett, M., & Kenny, P. A. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0709 · Cited by 56
Minimal residual disease in cancer therapy – Small things make all the difference
Blatter, S., & Rottenberg, S. (2015) · Drug Resistance Updates · doi:10.1016/j.drup.2015.08.003 · Cited by 55
Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGF/c-Met/Akt and Jak2/Stat3 Pathways
Chen, W., Wu, J., Shi, H., Wang, Z., Zhang, G., Cao, Y., Jiang, C., & Ding, Y. (2014) · BioMed Research International · doi:10.1155/2014/764981 · Cited by 56
Impairing Powerhouse in Colon Cancer Cells by Hydrazide–Hydrazone-Based Small Molecule
Patil, S., Kuman, M. M., Palvai, S., Sengupta, P., & Basu, S. (2018) · ACS Omega · doi:10.1021/acsomega.7b01512 · Cited by 55
Dissecting Mechanisms of Melanoma Resistance to BRAF and MEK Inhibitors Revealed Genetic and Non-Genetic Patient- and Drug-Specific Alterations and Remarkable Phenotypic Plasticity
Hartman, M. L., Sztiller-Sikorska, M., Gajos-Michniewicz, A., & Czyż, M. (2020) · Cells · doi:10.3390/cells9010142 · Cited by 57
Role of p38 mitogen‐activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs
Chander, Y., Kumar, R., Khandelwal, N., Singh, N., Shringi, B. N., Barua, S., & Kumar, N. (2021) · Reviews in Medical Virology · doi:10.1002/rmv.2217 · Cited by 56
Time resolved quantitative phospho-tyrosine analysis reveals Bruton’s Tyrosine kinase mediated signaling downstream of the mutated granulocyte-colony stimulating factor receptors
Dwivedi, P., Muench, D. E., Wagner, M., Azam, M., Grimes, H. L., & Greis, K. D. (2018) · Leukemia · doi:10.1038/s41375-018-0188-8 · Cited by 55
The MEK/ERK/miR-21 Signaling Is Critical in Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Cancer Cells
Huang, W.-C., Yadav, V. K., Cheng, W.-H., Wang, C., Hsieh, M., Huang, T., Lin, S., Yeh, C., & Kuo, K.-T. (2021) · Cancers · doi:10.3390/cancers13236005 · Cited by 55
Cabozantinib (XL184) Inhibits Growth and Invasion of Preclinical TNBC Models
Sameni, M., Tovar, E. A., Essenburg, C. J., Chalasani, A., Linklater, E. S., Borgman, A. S., Cherba, D., Anbalagan, A., Winn, M. E., Graveel, C. R., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0187 · Cited by 55
Bruton's Tyrosine Kinase Inhibitors Prevent Therapeutic Escape in Breast Cancer Cells
Wang, X., Wong, J., Sevinsky, C. J., Kokabee, L., Khan, F., Sun, Y., & Conklin, D. S. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0813 · Cited by 56
Adaptive Resistance to Dual BRAF/MEK Inhibition in BRAF-Driven Tumors through Autocrine FGFR Pathway Activation
Wang, V. E. H., Xue, J. Y., Frederick, D. T., Cao, Y., Lin, E., Wilson, C., Urisman, A., Carbone, D. P., Flaherty, K. T., Bernards, R., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2779 · Cited by 57
Melanoma: Clinical Features and Genomic InsightsPreprint
Hawryluk, E. B., & Tsao, H. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a015388 · Cited by 59
A Nexus Consisting of Beta-Catenin and Stat3 Attenuates BRAF Inhibitor Efficacy and Mediates Acquired Resistance to Vemurafenib
Sinnberg, T. W., Makino, E., Krueger, M. A., Velić, A., Maček, B., Rothbauer, U., Groll, N., Poetz, O., Czemmel, S., Niessner, H., et al. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.04.037 · Cited by 53
The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance
Diazzi, S., Tartare‐Deckert, S., & Deckert, M. (2023) · Oncogenesis · doi:10.1038/s41389-023-00452-8 · Cited by 61
Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition
Mok, S., Tsoi, J., Koya, R. C., Hu‐Lieskovan, S., West, B. L., Bollag, G. E., Graeber, T. G., & Ribas, A. (2015) · BMC Cancer · doi:10.1186/s12885-015-1377-8 · Cited by 54
Biomarkers of drugs targeting HER ‐family signalling in cancer
Montemurro, F., & Scaltriti, M. (2013) · The Journal of Pathology · doi:10.1002/path.4269 · Cited by 56
Hypoxia-Driven Mechanism of Vemurafenib Resistance in Melanoma
Qin, Y. W., Roszik, J., Chattopadhyay, C., Hashimoto, Y., Liu, C., Cooper, Z. A., Wargo, J. A., Hwu, P., Ekmekçioglu, S., & Grimm, E. A. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0963 · Cited by 54
HDAC inhibitors restore BRAF‐inhibitor sensitivity by altering PI3K and survival signalling in a subset of melanoma
Gallagher, S. J., Gunatilake, D., Beaumont, K. A., Sharp, D. M., Tiffen, J. C., Heinemann, A., Weninger, W., Haass, N. K., Wilmott, J. S., Madore, J., et al. (2017) · International Journal of Cancer · doi:10.1002/ijc.31199 · Cited by 56
Cytokine-mediated therapeutic resistance in breast cancer
Tan, C., Hu, W., He, Y., Zhang, Y., Zhang, G., Xu, Y., & Tang, J. (2018) · Cytokine · doi:10.1016/j.cyto.2018.03.020 · Cited by 57
Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer
Hutchinson, R. A., Adams, R., McArt, D. G., Salto‐Tellez, M., Jasani, B., & Hamilton, P. W. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0531-z · Cited by 57
PAK1 mediates pancreatic cancer cell migration and resistance to MET inhibition
Zhou, W., Jubb, A. M., Lyle, K. S., Xiao, Q., Ong, C. C., Desai, R. M., Fu, L. L., Gnad, F., Song, Q., Haverty, P. M., et al. (2014) · The Journal of Pathology · doi:10.1002/path.4412 · Cited by 53

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

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

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks