Cited by 1,771Melanoma and MAPK PathwaysCancer Cells and MetastasisColorectal Cancer Treatments and Studies

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Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

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Straussman, Ravid, Morikawa, Teppei, Shee, Kevin, Barzily-Rokni, Michal, Qian, Zhi Rong, Du, Jinyan, Davis, Ashli, Mongare, Margaret M., Gould, Joshua, Frederick, Dennie T., Cooper, Zachary A., Chapman, Paul B., Solit, David B., Ribas, Antoni, Lo, Roger S., Flaherty, Keith T., Ogino, Shuji, Wargo, Jennifer A., Golub, Todd R.·2012·Nature

DOI 10.1038/nature11183PMC PMC3711467

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Abstract

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)–AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.

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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
Self-citation
Fibroblasts in cancer
Kalluri, R., & Zeisberg, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1877 · Cited by 4,538
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
Microenvironmental regulation of metastasis
Joyce, J. A., & Pollard, J. W. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2618 · Cited by 3,684
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Flaherty, K. T., Puzanov, I., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., O'Dwyer, P. J., Lee, R. J., Grippo, J. F., Nolop, K., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002011 · Cited by 3,103
Self-citation
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
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Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib
Sosman, J. A., Kim, K. B., Schuchter, L., Gonzalez, R., Pavlick, A. C., Weber, J. S., McArthur, G. A., Hutson, T. E., Moschos, S. J., Flaherty, K. T., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1112302 · Cited by 2,156
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Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR
Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., Beijersbergen, R. L., Bardelli, A., & Bernards, R. (2012) · Nature · doi:10.1038/nature10868 · Cited by 2,051
Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
Bollag, G. E., Hirth, P., Tsai, J. Y., Zhang, J., Ibrahim, P. N., Cho, H., Spevak, W. R., Zhang, C., Zhang, Y., Habets, G. G. M., et al. (2010) · Nature · doi:10.1038/nature09454 · Cited by 1,875
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
Self-citation

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BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers
Castellani, G., Buccarelli, M., Arasi, M. B., Rossi, S., Pisanu, M. E., Bellenghi, M., Lintas, C., & Tabolacci, C. (2023) · Cancers · doi:10.3390/cancers15164026 · Cited by 210
Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1–MMP9 axis
Yan, X.-L., Jia, Y.-L., Chen, L., Zeng, Q., Zhou, J.-N., Fu, C.-J., Chen, H.-X., Yuan, H.-F., Li, Z.-W., Shi, L., et al. (2013) · Hepatology · doi:10.1002/hep.26257 · Cited by 185
Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells
Baenke, F., Chaneton, B., Smith, M., van den Broek, N. J. F., Hogan, K., Tang, H., Virós, A., Martin, M. J., Galbraith, L. C. A., Girotti, M. R., et al. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2015.08.003 · Cited by 191
B-cell precursor acute lymphoblastic leukemia cells use tunneling nanotubes to orchestrate their microenvironment
Polak, R., de Rooij, B., Pieters, R., & den Boer, M. L. (2015) · Blood · doi:10.1182/blood-2015-03-634238 · Cited by 188
Cancer systems biology: embracing complexity to develop better anticancer therapeutic strategies
Du, W., & Elemento, O. (2014) · Oncogene · doi:10.1038/onc.2014.291 · Cited by 185
Mesenchymal stroma: Role in osteosarcoma progression
Cortini, M., Avnet, S., & Baldini, N. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.07.024 · Cited by 171
A framework for understanding and targeting residual disease in oncogene-driven solid cancers
Bivona, T. G., & Doebele, R. C. (2016) · Nature Medicine · doi:10.1038/nm.4091 · Cited by 184
Lessons from patient-derived xenografts for better in vitro modeling of human cancer
Choi, S. Y. C., Lin, D., Gout, P. W., Collins, C. C., Xu, Y., & Wang, Y. Z. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.09.009 · Cited by 181
Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors
Djurec, M., Graña‐Castro, O., Lee, A., Troulé, K., Espinet, E., Cabras, L., Navas, C., Blasco, M. T., Martín-Díaz, L., Burdiel, M., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717802115 · Cited by 178
WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors
Anastas, J. N., Kulikauskas, R. M., Tamir, T. Y., Rizos, H., Long, G. V., von Euw, E. M., Yang, P., Chen, H., Haydu, L. E., Toroni, R. A., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci70156 · Cited by 184
Current Advances in the Treatment of BRAF-Mutant Melanoma
Patel, H. M., Yacoub, N., Mishra, R., White, A., Yuan, L., Alanazi, S., & Garrett, J. T. (2020) · Cancers · doi:10.3390/cancers12020482 · Cited by 184
A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer
Wilson, F. H., Johannessen, C. M., Piccioni, F., Tamayo, P., Kim, J. W., Allen, E. M. V., Corsello, S. M., Capelletti, M., Calles, A., Butaney, M., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.02.005 · Cited by 178
Mitochondria: gatekeepers of response to chemotherapy
Sarosiek, K. A., Chonghaile, T. N., & Letai, A. G. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.08.003 · Cited by 177
The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF
Watson, I. R., Li, L., Cabeceiras, P. K., Mahdavi, M., Gutschner, T., Genovese, G., Wang, G., Fang, Z., Tepper, J. M., Stemke‐Hale, K., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1232-t · Cited by 173
PTPN11 is a central node in intrinsic and acquired resistance to targeted cancer drugs
Prahallad, A., Heynen, G. J. J. E., Germano, G., Willems, S. M., Evers, B., Vecchione, L., Gambino, V., Lieftink, C., Beijersbergen, R. L., Di Nicolantonio, F., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.037 · Cited by 168
Developments in preclinical cancer imaging: innovating the discovery of therapeutics
Conway, J. R. W., Carragher, N. O., & Timpson, P. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3724 · Cited by 165
Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target
Amirouchene-Angelozzi, N., Némati, F., Gentien, D., Nicolas, A., Dumont, A. G., Carita, G., Camonis, J., Desjardins, L., Cassoux, N., Piperno-Neumann, S., et al. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.06.004 · Cited by 167
Immune Effects of Chemotherapy, Radiation, and Targeted Therapy and Opportunities for Combination With Immunotherapy
Wargo, J. A., Reuben, A., Cooper, Z. A., Oh, K. S., & Sullivan, R. J. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.05.007 · Cited by 172
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Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance
Miller, M. A., Oudin, M. J., Sullivan, R. J., Wang, S. J., Meyer, A. S., Im, H., Frederick, D. T., Tadros, J., Griffith, L. G., Lee, H., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0933 · Cited by 168
Self-citation
FGF2 from Marrow Microenvironment Promotes Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia
Traer, E. A., Martinez, J., Javidi‐Sharifi, N., Agarwal, A., Dunlap, J. B., English, I. A., Kovacsovics, T. J., Tyner, J. W., Wong, M. H., & Druker, B. J. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3569 · Cited by 168
Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity
Ilkow, C. S., Marguerie, M., Batenchuk, C., Mayer, J., Ben Neriah, D., Cousineau, S., Falls, T., Jennings, V. A., Boileau, M., Bellamy, D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3848 · Cited by 165
Capmatinib (INC280) Is Active Against Models of Non–Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation
Baltschukat, S., Engstler, B. S., Huang, A., Hao, H.-X., Tam, A., Wang, H. Q., Liang, J., DiMare, M. T., Bhang, H.-E. C., Wang, Y., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2814 · Cited by 167
Noninvasive Detection of Activating Estrogen Receptor 1 (ESR1) Mutations in Estrogen Receptor–Positive Metastatic Breast Cancer
Guttery, D. S., Page, K., Hills, A., Woodley, L., Marchese, S. D., Rghebi, B., Hastings, R. K., Luo, J., Pringle, J. H., Stebbing, J., et al. (2015) · Clinical Chemistry · doi:10.1373/clinchem.2015.238717 · Cited by 170
Phenotype Switching in Melanoma: Implications for Progression and Therapy
Li, F. Z., Dhillon, A. S., Anderson, R. L., McArthur, G. A., & Ferrao, P. T. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00031 · Cited by 164
Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy
Tavora, B., Reynolds, L. E., Batista, S., Demircioglu, F., Fernandez, I., Lechertier, T., Lees, D. M., Wong, P.-P., Alexopoulou, A., Elia, G., et al. (2014) · Nature · doi:10.1038/nature13541 · Cited by 163
Gold Nanoparticle Reprograms Pancreatic Tumor Microenvironment and Inhibits Tumor Growth
Saha, S., Xiong, X., Chakraborty, P. K., Shameer, K., Arvizo, R. R., Kudgus, R. A., Dwivedi, S. K. D., Hossen, M. N., Gillies, E. M., Robertson, J. D., et al. (2016) · ACS Nano · doi:10.1021/acsnano.6b02231 · Cited by 166
MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale
Salgia, R. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0472 · Cited by 162
Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma
Lim, S. Y., Menzies, A. M., & Rizos, H. (2017) · Cancer · doi:10.1002/cncr.30435 · Cited by 169
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Sánchez‐López, E., Flashner-Abramson, E., Shalapour, S., Zhong, Z., Taniguchi, K., Levitzki, A., & Karin, M. (2015) · Oncogene · doi:10.1038/onc.2015.326 · Cited by 160
BRAF-mutant melanoma: treatment approaches, resistance mechanisms, and diagnostic strategies
Spagnolo, F., Ghiorzo, P., Orgiano, L., Pastorino, L., Picasso, V., Tornari, E., Ottaviano, V., & Queirolo, P. (2015) · OncoTargets and Therapy · doi:10.2147/ott.s39096 · Cited by 163
Dabrafenib and its potential for the treatment of metastatic melanoma
Murali, R., Menzies, A. M., & Long, G. V. (2012) · Drug Design Development and Therapy · doi:10.2147/dddt.s38998 · Cited by 165
Feedback and redundancy in receptor tyrosine kinase signaling: relevance to cancer therapies
Sun, C., & Bernards, R. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.08.010 · Cited by 155
Optimization of liquid overlay technique to formulate heterogenic 3D co-cultures models
Costa, E. C., Gaspar, V. M., Coutinho, P., & Correia, I. J. (2014) · Biotechnology and Bioengineering · doi:10.1002/bit.25210 · Cited by 156
Modeling human carcinomas: Physiologically relevant 3D models to improve anti-cancer drug development
Unger, C., Kramer, N., Walzl, A., Scherzer, M., Hengstschläger, M., & Dolznig, H. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.10.015 · Cited by 158
Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target
Togo, S., Polanska, U. M., Horimoto, Y., & Orimo, A. (2013) · Cancers · doi:10.3390/cancers5010149 · Cited by 162
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition
Glaviano, A., Lau, H., Carter, L. M., Lee, E. H. C., Lam, H. Y., Okina, E., Tan, D. J. J., Tan, W., Ang, H. L., Carbone, D., et al. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01634-6 · Cited by 169
The Gastrointestinal Tumor Microenvironment
Quante, M., Varga, J., Wang, T. C., & Greten, F. R. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.03.052 · Cited by 154
MAP kinase signaling and inhibition in melanoma
Sullivan, R. J., & Flaherty, K. T. (2012) · Oncogene · doi:10.1038/onc.2012.345 · Cited by 162
Self-citation
The bone-marrow niche in MDS and MGUS: implications for AML and MM
Ghobrial, I. M., Detappe, A., Anderson, K. C., & Steensma, D. P. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.197 · Cited by 156
Precise role of dermal fibroblasts on melanocyte pigmentation
Wang, Y., Viennet, C., Robin, S., Berthon, J., He, L., & Humbert, P. G. (2017) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2017.06.018 · Cited by 153
The roles of microphthalmia-associated transcription factor and pigmentation in melanoma
Hsiao, J. J., & Fisher, D. E. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.07.019 · Cited by 148
Tumor-associated B-cells induce tumor heterogeneity and therapy resistance
Somasundaram, R., Zhang, G., Fukunaga-Kalabis, M., Perego, M., Krepler, C., Xu, X., Wagner, C., Hristova, D., Zhang, J., Tian, T., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00452-4 · Cited by 151
Self-citation
Exploring the Tumor Microenvironment with Nanoparticles
Miao, L., & Huang, L. (2015) · Cancer treatment and research · doi:10.1007/978-3-319-16555-4_9 · Cited by 155
Microenvironment-Driven Dynamic Heterogeneity and Phenotypic Plasticity as a Mechanism of Melanoma Therapy Resistance
Ahmed, F., & Haass, N. K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00173 · Cited by 153
The MAPK (ERK) Pathway: Investigational Combinations for the Treatment Of BRAF-Mutated Metastatic Melanoma.
McCain, J. (2013) · Europe PMC (PubMed Central) · Cited by 146
MET signaling in colon cancer stem-like cells blunts the therapeutic response to EGFR inhibitors.
Luraghi, P., Reato, G., Cipriano, E., Sassi, F., Orzan, F., Bigatto, V., De Bacco, F., Menietti, E., Han, M., Rideout, W. M., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2340-t · Cited by 146
Overcoming EMT-associated resistance to anti-cancer drugs via Src/FAK pathway inhibition
WILSON, C. A., Nicholes, K., Bustos, D. J., Lin, E., Song, Q., Stéphan, J.-P., Kirkpatrick, D. S., & Settleman, J. (2014) · Oncotarget · doi:10.18632/oncotarget.2397 · Cited by 149
Cancer-associated fibroblasts: how do they contribute to metastasis?
Kwa, M. Q., Herum, K. M., & Brakebusch, C. (2019) · Clinical & Experimental Metastasis · doi:10.1007/s10585-019-09959-0 · Cited by 150
Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma: A Systematic Review
Proietti, I., Skroza, N., Bernardini, N., Tolino, E., Balduzzi, V., Marchesiello, A., Michelini, S., Volpe, S., Mambrin, A., Mangino, G., et al. (2020) · Cancers · doi:10.3390/cancers12102801 · Cited by 153
Tumor Microenvironment: Implications in Melanoma Resistance to Targeted Therapy and Immunotherapy
Falcone, I., Conciatori, F., Bazzichetto, C., Ferretti, G., Cognetti, F., Ciuffreda, L., & Milella, M. (2020) · Cancers · doi:10.3390/cancers12102870 · Cited by 151
Stromal-Immune Score Based Gene Signature: A Prognosis Stratification Tool in Gastric Cancer
Wang, H., Wu, X., & Chen, Y. (2019) · Frontiers in Oncology · doi:10.2139/ssrn.3409287 · Cited by 144
Similar but different: distinct roles for KRAS and BRAF oncogenes in colorectal cancer development and therapy resistance
Morkel, M., Riemer, P., Bläker, H., & Sers, C. (2015) · Oncotarget · doi:10.18632/oncotarget.4750 · Cited by 146
Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment
Herrmann, D., Conway, J. R. W., Vennin, C., Magenau, A., Hughes, W. E., Morton, J. P., & Timpson, P. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu108 · Cited by 144
Tumor-Associated Macrophages Suppress the Cytotoxic Activity of Antimitotic Agents
Olson, O. C., Kim, H.-J., Quail, D. F., Foley, E. A., & Joyce, J. A. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.038 · Cited by 149
Comprehensively priming the tumor microenvironment by cancer-associated fibroblast-targeted liposomes for combined therapy with cancer cell-targeted chemotherapeutic drug delivery system
Chen, B., Dai, W., Mei, D., Liu, T., Li, S., He, B., He, B., Yuan, L., Zhang, H., Wang, X., et al. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.09.014 · Cited by 142
TORC1 Suppression Predicts Responsiveness to RAF and MEK Inhibition in BRAF- Mutant Melanoma
Corcoran, R. B., Rothenberg, S. M., Hata, A. N., Faber, A. C., Piris, A., Nazarian, R. M., Brown, R. D., Godfrey, J. T., Winokur, D., Walsh, J., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005753 · Cited by 140
Self-citation
Sorafenib resistance and JNK signaling in carcinoma during extracellular matrix stiffening
Nguyen, T. V., Sleiman, M., Moriarty, T., Herrick, W. G., & Peyton, S. R. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.03.058 · Cited by 142
Fibroblast-mediated drug resistance in cancer
Paraiso, K. H. T., & Smalley, K. S. M. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.01.018 · Cited by 147
Systemic treatment for BRAF-mutant melanoma: where do we go next?
Menzies, A. M., & Long, G. V. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70072-5 · Cited by 145
SPARC independent drug delivery and antitumour effects of nab -paclitaxel in genetically engineered mice
Neeße, A., Frese, K. K., Chan, D. S., Bapiro, T. E., Howat, W., Richards, F. M., Ellenrieder, V., Jodrell, D. I., & Tuveson, D. A. (2013) · Gut · doi:10.1136/gutjnl-2013-305559 · Cited by 141
Immune-mediated mechanisms influencing the efficacy of anticancer therapies
Coffelt, S. B., & de Visser, K. E. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.006 · Cited by 147
Combination antitumor therapy with targeted dual-nanomedicines
Dai, W., Wang, X., Song, G., Liu, T., He, B., Zhang, H., Wang, X., & Zhang, Q. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.03.001 · Cited by 139
Bone marrow stroma‐mediated resistance to FLT 3 inhibitors in FLT 3‐ ITD AML is mediated by persistent activation of extracellular regulated kinase
Yang, X., Sexauer, A. N., & Levis, M. J. (2013) · British Journal of Haematology · doi:10.1111/bjh.12599 · Cited by 139
Cancer Drug Resistance: A Brief Overview from a Genetic Viewpoint
Rueff, J., & Rodrigues, A. S. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3347-1_1 · Cited by 144
The mitogen-activated protein kinase pathway in melanoma part I – Activation and primary resistance mechanisms to BRAF inhibition
Amaral, T. M. S., Sinnberg, T. W., Meier, F. E., Krepler, C., Levesque, M. P., Niessner, H., & Garbe, C. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2016.12.010 · Cited by 138
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Yao, M., Ventura, P. B., Jiang, Y., Rodriguez, F. J., Wang, L., Perry, J. S. A., Yang, Y., Wahl, K., Crittenden, R. B., Bennett, M. L., et al. (2020) · Cell · doi:10.1016/j.cell.2019.12.024 · Cited by 133
The CDK4/6 inhibitor LY2835219 overcomes vemurafenib resistance resulting from MAPK reactivation and cyclin D1 upregulation
Yadav, V., Burke, T. F., Huber, L., Van Horn, R. D., Zhang, Y., Buchanan, S. G., Chan, E. M., Starling, J. J., Beckmann, R. P., & Peng, S.-B. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0257 · Cited by 132
c-Met as a Target for Personalized Therapy
Garajová, I., Giovannetti, E., Biasco, G., & Peters, G. J. (2015) · Translational Oncogenomics · doi:10.4137/tog.s30534 · Cited by 141
BRAF — a tumour-agnostic drug target with lineage-specific dependencies
Hanrahan, A. J., Chen, Z., Rosen, N., & Solit, D. B. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00852-0 · Cited by 136
Self-citation
Mathematical modeling and computational prediction of cancer drug resistance
Sun, X., & Hu, B. X. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbx065 · Cited by 142
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Authors: Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z. R., Du, J., Davis, A., Mongare, M. M., Gould, J., Frederick, D. T., Cooper, Z. A., Chapman, P. B., Solit, D. B., Ribas, A., Lo, R. S., Flaherty, K. T., Ogino, S., Wargo, J. A., & Golub, T. R.
Affiliations: Broad Institute (US)
Dana-Farber Cancer Institute (US)
Massachusetts General Hospital (US)
Memorial Sloan Kettering Cancer Center (US)
University of California, Los Angeles (US)
Brigham and Women's Hospital (US)
Corresponding author: Golub, Todd R.
ORCID: Straussman, Ravid
Morikawa, Teppei
Shee, Kevin
Barzily-Rokni, Michal
Qian, Zhi Rong
Gould, Joshua
Frederick, Dennie T.
Cooper, Zachary A.
Chapman, Paul B.
Solit, David B.
Ribas, Antoni
Lo, Roger S.
Flaherty, Keith T.
Ogino, Shuji
Wargo, Jennifer A.
Golub, Todd R.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2012-07
Volume: 487
Issue: 7408
Pages: 500-504
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature11183
PMC: PMC3711467
OpenAlex: W2055624262
Semantic Scholar: d51bc0a1730710ad5e74705bff1a2f756c61fc28
Cited by: 1,771
References: 30
Citations by year: 2026: 51 · 2025: 48 · 2024: 68 · 2023: 93 · 2022: 98 · 2021: 102 · 2020: 114 · 2019: 115 · 2018: 138 · 2017: 150 · 2016: 154 · 2015: 172 · 2014: 215 · 2013: 196 · 2012: 53
FWCI: 82.21
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
eScholarship (California Digital Library) (submittedVersion)
Funders: Howard Hughes Medical Institute
National Cancer Institute (R01CA166480, U54CA112962, P50CA093683, UM1CA186709)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords: RAF inhibitors, vemurafenib, drug resistance, tumor microenvironment, stromal cells, hepatocyte growth factor, MAPK signaling, PI3K/Akt signaling, combination therapy, co-culture model, targeted therapy, non-specific immunity, cancer cell lines, proteomics, immunohistochemistry, immunofluorescence
MeSH terms: Vemurafenib, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Humans, Indoles, Melanoma, Mutation, Prognosis, Sulfonamides, Signal Transduction, Stromal Cells, Hepatocyte Growth Factor, Coculture Techniques, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Phosphatidylinositol 3-Kinases, Proteomics, Cell Line, Tumor, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf, Molecular Targeted Therapy, Tumor Microenvironment

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