Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120
Published version of a preprint
Abstract
We have identified previously undiscovered BRAF in-frame deletions near the αC-helix region of the kinase domain in pancreatic, lung, ovarian, and thyroid cancers. These deletions are mutually exclusive with KRAS mutations and occur in 4.21% of KRAS wild-type pancreatic cancer. siRNA knockdown in cells harboring BRAF deletions showed that the MAPK activity and cell growth are BRAF dependent. Structurally, the BRAF deletions are predicted to shorten the β3/αC-helix loop and hinder its flexibility by locking the helix in the active αC-helix-in conformation that favors dimer formation. Expression of L485-P490–deleted BRAF is able to transform NIH/3T3 cells in a BRAF dimer–dependent manner. BRAF homodimer is confirmed to be the dominant RAF dimer by proximity ligation assays in BRAF deletion cells, which are resistant to the BRAF inhibitor vemurafenib and sensitive to LY3009120, a RAF dimer inhibitor. In tumor models with BRAF deletions, LY3009120 has shown tumor growth regression, whereas vemurafenib is inactive. Significance: This study discovered oncogenic BRAF deletions with a distinct activation mechanism dependent on the BRAF dimer formation in tumor cells. LY3009120 is active against these cells and represents a potential treatment option for patients with cancer with these BRAF deletions, or other atypical BRAF mutations where BRAF functions as a dimer. Cancer Discov; 6(3); 300–15. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 217
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KRAS wild type PDAC, including BxPC3, acquire in-frame deletions of BRAF that result in constitutive activation of the kinase domain.
“It is known that in contrast to melanoma, cases of KRAS wild type PDAC, including the BxPC3 cell line itself, acquire in-frame deletions of BRAF that result in constitutive activation of the kinase domain (Chen 2016)15.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as Chen 2016)15
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 · see citing works
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674 · see citing works
<i>EGFR</i> 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 · see citing works
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 · see citing works
Inhibition of Mutated, Activated BRAF in Metastatic Melanoma
Flaherty, K. T., Puzanov, I. J., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., O'Dwyer, P. J., Lee, R. J., Grippo, J. F., Nolop, K. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002011 · Cited by 3,542 · see citing works
Discovery and saturation analysis of cancer genes across 21 tumour types
Lawrence, M. S., Stojanov, P., Mermel, C. H., Robinson, J. T., Garraway, L. A., Golub, T. R., Meyerson, M., Gabriel, S. B., Lander, E. S., & Getz, G. (2014) · Nature · doi:10.1038/nature12912 · Cited by 3,096 · see citing works
Hauschild, A., Grob, J., Демидов, Л. В., Jouary, T., Gutzmer, R., Millward, M. J., Rutkowski, P. L., Blank, C. U., Miller, W. H., Kaempgen, E., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60868-x · Cited by 2,975 · see citing works
Mechanism of Activation of the RAF-ERK Signaling Pathway by Oncogenic Mutations of B-RAF
Wan, P., Garnett, M. J., Roe, S. M., Lee, S., Niculescu‐Duvaz, D., Good, V. M., Cancer Genome Project, Jones, C. M., Marshall, C. J., Springer, C. J., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00215-6 · Cited by 2,800 · see citing works
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278 · see citing works
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 1,841 · see citing works
Self-citationRAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF
Poulikakos, P. I., Zhang, C., Bollag, G. E., Shokat, K. M., & Rosen, N. X. (2010) · Nature · doi:10.1038/nature08902 · Cited by 1,818 · see citing works
RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
Hatzivassiliou, G., Song, K. W., Yen, I., Brandhuber, B. J., Anderson, D. J., Alvarado, R., Ludlam, M. J. C., Stokoe, D., Gloor, S. L., Vigers, G. P. A., et al. (2010) · Nature · doi:10.1038/nature08833 · Cited by 1,614 · see citing works
Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF
Heidorn, S. J., Milagre, C. S., Whittaker, S. R., Nourry, A., Niculescu‐Duvaz, I., Dhomen, N. S., Hussain, J., Reis-Filho, J. S., Springer, C. J., Pritchard, C. A., et al. (2010) · Cell · doi:10.1016/j.cell.2009.12.040 · Cited by 1,468 · see citing works
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Poulikakos, P. I., Persaud, Y., Janakiraman, M., Kong, X., Ng, C., Moriceau, G., Shi, H., Atefi, M., Titz, B., Gabay, M. T., et al. (2011) · Nature · doi:10.1038/nature10662 · Cited by 1,454 · see citing works
The RAF proteins take centre stage
Wellbrock, C., Karasarides, M., & Marais, R. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1498 · Cited by 1,233 · see citing works
Recurrent BRAF mutations in Langerhans cell histiocytosis
Badalian‐Very, G., Vergilio, J., Degar, B. A., MacConaill, L. E., Brandner, B., Calicchio, M. L., Kuo, F. C., Ligon, A. H., Stevenson, K. E., Kehoe, S. M., et al. (2010) · Blood · doi:10.1182/blood-2010-04-279083 · Cited by 1,232 · see citing works
The landscape of kinase fusions in cancer
Stransky, N., Cerami, E., Schalm, S., Kim, J. L., & Lengauer, C. (2014) · Nature Communications · doi:10.1038/ncomms5846 · Cited by 968 · see citing works
Jones, D., Kocialkowski, S., Liu, L., Pearson, D. M., Bäcklund, L. M., Ichimura, K., & Collins, V. P. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2097 · Cited by 938 · see citing works
Activating HER2 Mutations in HER2 Gene Amplification Negative Breast Cancer
Bose, R., Kavuri, S. M., Searleman, A. C., Shen, W., Shen, D., Koboldt, D. C., Monsey, J. D., Goel, N. J., Aronson, A. B., Li, S., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0349 · Cited by 869 · see citing works
Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond
Holderfield, M. T., Deuker, M. M., McCormick, F. P., & McMahon, M. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3760 · Cited by 828 · see citing works
Garnett, M. J., & Marais, R. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.09.022 · Cited by 799 · see citing works
Tumor adaptation and resistance to RAF inhibitors
Lito, P., Rosen, N., & Solit, D. B. (2013) · Nature Medicine · doi:10.1038/nm.3392 · Cited by 585 · see citing works
Lito, P., Pratilas, C. A., Joseph, E. W., Tadi, M., Halilovic, E., Zubrowski, M., Huang, A., Wong, W. L., Callahan, M. K., Merghoub, T., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.10.009 · Cited by 562 · see citing works
Yao, Z., Torres, N. M., Tao, A., Gao, Y., Luo, L., Li, Q., de Stanchina, E., Abdel-Wahab, O., Solit, D. B., Poulikakos, P. I., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.08.001 · Cited by 543 · see citing works
A dimerization-dependent mechanism drives RAF catalytic activation
Rajakulendran, T., Sahmi, M., Lefrançois, M., Sicheri, F., & Therrien, M. (2009) · Nature · doi:10.1038/nature08314 · Cited by 492 · see citing works
Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma
Palanisamy, N., Ateeq, B., Sundaram, S. K., Pflueger, D., Ramnarayanan, K., Shankar, S., Han, B., Cao, Q., Cao, X., Suleman, K., et al. (2010) · Nature Medicine · doi:10.1038/nm.2166 · Cited by 460 · see citing works
Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer
Ciampi, R., Knauf, J. A., Kerler, R., Gandhi, M., Zhu, Z., Nikiforova, M. N., Rabes, H. M., Fagin, J. A., & Nikiforov, Y. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23237 · Cited by 459 · see citing works
Yuen, S. T., Davies, H. R., Chan, T. L., Ho, J. W. C., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Tsui, W. W., Chan, A. S. Y., et al. (2002) · PubMed · Cited by 410 · see citing works
Yang, H. Y., Higgins, B., Kolinsky, K. D., Packman, K. E., Go, Z., Iyer, R. M., Kolis, S. P., Zhao, S., Lee, R., Grippo, J. F., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0646 · Cited by 408 · see citing works
V599EB-RAF is an Oncogene in Melanocytes
Wellbrock, C., Ogilvie, L. M., Hedley, D., Karasarides, M., Martin, J., Niculescu‐Duvaz, D., Springer, C. J., & Marais, R. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3433 · Cited by 344 · see citing works
Peng, S.-B., Henry, J. R., Kaufman, M. D., Lu, W.-P., Smith, B. D., Vogeti, S., Rutkoski, T. J., Wise, S., Chun, L., Zhang, Y., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.08.002 · Cited by 298 · see citing works
Self-citationGreaves, W. O., Verma, S., Patel, K. P., Davies, M. A., Barkoh, B. A., Galbincea, J. M., Yao, H., Lazar, A. J., Aldape, K., Medeiros, L. J., et al. (2012) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2012.10.002 · Cited by 226 · see citing works
King, A. J., Arnone, M. R., Bleam, M. R., Moss, K. G., Yang, J., Fedorowicz, K. E., Smitheman, K. N., Erhardt, J. A., Hughes‐Earle, A., Kane-Carson, L. S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067583 · Cited by 223 · see citing works
Effects of Raf Dimerization and Its Inhibition on Normal and Disease-Associated Raf Signaling
Freeman, A. K., Ritt, D. A., & Morrison, D. K. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.12.018 · Cited by 201 · see citing works
Yadav, V., Zhang, X., Liu, J., Estrem, S., Li, S., Gong, X.-Q., Buchanan, S., Henry, J. R., Starling, J. J., & Peng, S.-B. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.377218 · Cited by 200 · see citing works
Self-citationHutchinson, K. E., Lipson, D., Stephens, P. J., Otto, G. A., Lehmann, B. D., Lyle, P. L., Vnencak‐Jones, C. L., Ross, J. S., Pietenpol, J. A., Sosman, J. A., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1746 · Cited by 182 · see citing works
Ikenoue, T., Hikiba, Y., Kanai, F., Tanaka, Y., Imamura, J., Imamura, T., Ohta, M., Ijichi, H., Tateishi, K., Kawakami, T., et al. (2003) · PubMed · Cited by 164 · see citing works
Röring, M., Herr, R., Fiala, G. J., Heilmann, K., Braun, S. L., Eisenhardt, A. E., Halbach, S., Capper, D., von Deimling, A., Schamel, W. W. A., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.100 · Cited by 138 · see citing works
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 · see citing works
Self-citationSánchez‐Laorden, B. L., Virós, A., Girotti, M. R., Pedersen, M., Saturno, G., Zambon, A., Niculescu‐Duvaz, D., Turajlic, S., Hayes, A. J., Gore, M. E., et al. (2014) · Science Signaling · doi:10.1126/scisignal.2004815 · Cited by 128 · see citing works
BRAF inhibitors in cancer therapy
Johansson, C. H., & Brage, S. E. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.11.011 · Cited by 112 · see citing works
Tiacci, E., Schiavoni, G., Martelli, M. P., Boveri, E., Pacini, R., Tabarrini, A., Zibellini, S., Santi, A., Pettirossi, V., Fortini, E., et al. (2013) · Haematologica · doi:10.3324/haematol.2012.078071 · Cited by 91 · see citing works
Henry, J. R., Kaufman, M. D., Peng, S.-B., Ahn, Y. M., Caldwell, T. M., Vogeti, L., Telikepalli, H., Lu, W.-P., Hood, M. M., Rutkoski, T. J., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00067 · Cited by 86 · see citing works
Self-citationAndreadi, C., Cheung, L.-K. M., Giblett, S. M., PATEL, B., Jin, H., Mercer, K., Kamata, T., Lee, P., Williams, A. G., McMahon, M., et al. (2012) · Genes & Development · doi:10.1101/gad.193458.112 · Cited by 66 · see citing works
Fichter, C. D., Timme, S., Braun, J. A., Gudernatsch, V., Schöpflin, A., Bogatyreva, L., Geddert, H., Faller, G., Klimstra, D. S., Tang, L. H., et al. (2014) · International Journal of Cancer · doi:10.1002/ijc.28771 · Cited by 58 · see citing works
Lee, N. V., Lira, M. E., Pavlı́ček, A., Ye, J., Buckman, D., Bagrodia, S., Srinivasa, S. P., Zhao, Y., Aparicio, S. A. J. R., Rejto, P. A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039653 · Cited by 50 · see citing works
Conformation-Specific Effects of Raf Kinase Inhibitors
Wang, X., & Kim, J. Y. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300613w · Cited by 49 · see citing works
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Integrated genomic characterization of pancreatic ductal adenocarcinoma
Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.007 · Cited by 2,019 · see citing works
KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer
Waters, A. M., & Der, C. J. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031435 · Cited by 875 · see citing works
Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer
Bryant, K. L., Stalnecker, C. A., Zeitouni, D., Klomp, J. E., Peng, S., Tikunov, A. P., Gunda, V., Pierobon, M., Waters, A. M., George, S. D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0368-8 · Cited by 692 · see citing works
Self-citationTumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS
Yao, Z., Yaeger, R., Rodrik-Outmezguine, V. S., Tao, A., Torres, N. M., Chang, M. T., Drosten, M., Zhao, H., Cecchi, F., Hembrough, T., et al. (2017) · Nature · doi:10.1038/nature23291 · Cited by 562 · see citing works
Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations
Dankner, M., Rose, A. A. N., Rajkumar, S., Siegel, P. M., & Watson, I. R. (2018) · Oncogene · doi:10.1038/s41388-018-0171-x · Cited by 553 · see citing works
Targeting Alterations in the RAF–MEK Pathway
Yaeger, R. D., & Corcoran, R. B. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1321 · Cited by 474 · see citing works
New perspectives for targeting RAF kinase in human cancer
Karoulia, Z., Gavathiotis, E., & Poulikakos, P. I. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.79 · Cited by 404 · see citing works
Papke, B., & Der, C. J. (2017) · Science · doi:10.1126/science.aam7622 · Cited by 399 · see citing works
From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer
Nevala-Plagemann, C., Hidalgo, M. M., & Garrido‐Laguna, I. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0281-6 · Cited by 391 · see citing works
Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine
Aguirre, A. J., Nowak, J. A., Camarda, N. D., Moffitt, R. A., Ghazani, A. A., Hazar-Rethinam, M., Raghavan, S., Kim, J., Brais, L. K., Ragon, D., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0275 · Cited by 367 · see citing works
Singhi, A. D., George, B., Greenbowe, J. R., Chung, J., Suh, J., Maitra, A., Klempner, S. J., Hendifar, A., Milind, J. M., Golan, T., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.02.037 · Cited by 348 · see citing works
Translational advances in pancreatic ductal adenocarcinoma therapy
Hosein, A. N., Dougan, S. K., Aguirre, A. J., & Maitra, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00349-2 · Cited by 249 · see citing works
Karoulia, Z., Wu, Y., Ahmed, T. A., Xin, Q., Bollard, J., Krepler, C., Wu, X., Zhang, C., Bollag, G. E., Herlyn, M., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.06.024 · Cited by 208 · see citing works
Targeting oncogenic Raf protein-serine/threonine kinases in human cancers
Roskoski, R. J. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.08.013 · Cited by 198 · see citing works
KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism
Vaseva, A. V., Blake, D. R., Gilbert, T. S. K., Ng, S., Hostetter, G. H., Azam, S. H., Ozkan‐Dagliyan, I., Gautam, P., Bryant, K. L., Pearce, K. H., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.10.001 · Cited by 181 · see citing works
Singhi, A. D., Nikiforova, M. N., Chennat, J. S., Papachristou, G. I., Khalid, A., Rabinovitz, M., Das, R. K., Sarkaria, S., Ayasso, M. S., Wald, A. I., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-317817 · Cited by 177 · see citing works
Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis
Chakraborty, R., Burke, T. M., Hampton, O. A., Zinn, D. J., Lim, K. P. H., Abhyankar, H. A., Scull, B., Kumar, V., Kakkar, N., Wheeler, D. A., et al. (2016) · Blood · doi:10.1182/blood-2016-08-733790 · Cited by 170 · see citing works
BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors
Schreck, K. C., Grossman, S. A., & Pratilas, C. A. (2019) · Cancers · doi:10.3390/cancers11091262 · Cited by 148 · see citing works
Molecular Pathways and Mechanisms of BRAF in Cancer Therapy
Poulikakos, P. I., Sullivan, R. J., & Yaeger, R. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-2138 · Cited by 145 · see citing works
Xiang, Y., Liu, X., Wang, Y., Zheng, D., Meng, Q., Jiang, L., Yang, S., Zhang, S., Zhang, X., Liu, Y., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1366260 · Cited by 146 · see citing works
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 · see citing works
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Molecular targeted therapy of BRAF -mutant colorectal cancer
Ducreux, M. P., Chamseddine, A. N., Laurent‐Puig, P., Smolenschi, C., Hollebecque, A., Dartigues, P., Samalin, E., Boige, V., Malka, D., & Gelli, M. (2019) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835919856494 · Cited by 99 · see citing works
Lee, L. H., Gasilina, A., Roychoudhury, J., Clark, J. P., McCormack, F. X., Pressey, J. G., Grimley, M. S., Lorsbach, R. B., Ali, S. M., Bailey, M., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.89473 · Cited by 96 · see citing works
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Sullivan, R. J., Hollebecque, A., Flaherty, K. T., Shapiro, G. I., Rodon, J. A., Millward, M., Zhang, W., Gao, L., Sykes, A. K., Willard, M. D., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0681 · Cited by 88 · see citing works
Self-citationThe genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma
Vo, J. N., Wu, Y., Mishler, J., Hall, S., Mannan, R., Wang, L., Yu, N., Zhou, J. R., Hopkins, A. C., Estill, J. C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31430-0 · Cited by 92 · see citing works
Anderson, G. R., Winter, P. S., Lin, K. H., Nussbaum, D. P., Cakir, M., Stein, E. M., Soderquist, R. S., Crawford, L., Leeds, J. C., Newcomb, R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.07.006 · Cited by 80 · see citing works
Nunno, V. D., Gatto, L., Tosoni, A., Bartolini, S., & Franceschi, E. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1067252 · Cited by 77 · see citing works
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Chen, S.-H., Gong, X., Zhang, Y., Horn, R. D. V., Yin, T., Huber, L., Burke, T., Manro, J. R., Iversen, P. W., Wu, W., et al. (2017) · Oncogene · doi:10.1038/onc.2017.384 · Cited by 72 · see citing works
Self-citationRAF kinase dimerization: implications for drug discovery and clinical outcomes
Brummer, T., & McInnes, C. (2020) · Oncogene · doi:10.1038/s41388-020-1263-y · Cited by 72 · see citing works
Jain, P., Fierst, T. M., Han, H. J., Smith, T. L., Vakil, A., Storm, P. B., Resnick, A. C., & Waanders, A. J. (2017) · Oncogene · doi:10.1038/onc.2017.276 · Cited by 72 · see citing works
A Secondary Mutation in BRAF Confers Resistance to RAF Inhibition in a BRAF V600E-Mutant Brain Tumor
Wang, J., Yao, Z., Jonsson, P., Allen, A. N., Qin, A. C. R., Uddin, S., Dunkel, I. J., Petriccione, M., Manova, K., Haque, S. S., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1263 · Cited by 68 · see citing works
Signaling from RAS to RAF: The Molecules and Their Mechanisms
Jeon, H., Tkacik, E., & Eck, M. J. (2024) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052521-040754 · Cited by 64 · see citing works
Chapeau, E. A., Gembarska, A., Durand, E. Y., Mandon, E., Estadieu, C., Romanet, V., Wiesmann, M., Tiedt, R., Lehar, J., de Weck, A., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620262114 · Cited by 64 · see citing works
Treatment outcomes and prognostic factors of patients with adult Langerhans cell histiocytosis
Cao, X., Duan, M., Zhao, A., Cai, H., Chen, J., Gao, X., Liu, T., Cai, H., Zhang, L., Sun, J. H., et al. (2021) · American Journal of Hematology · doi:10.1002/ajh.26412 · Cited by 60 · see citing works
Activating mutations in MEK1 enhance homodimerization and promote tumorigenesis
Yuan, J., Ng, W. H., Tian, Z., Yap, J., Baccarini, M., Chen, Z., & Hu, J. (2018) · Science Signaling · doi:10.1126/scisignal.aar6795 · Cited by 59 · see citing works
Targeted therapy and drug resistance in thyroid cancer
Zhang, Y., Xing, Z., Liu, T., Tang, M., Mi, L., Zhu, J., Wu, W., & Wei, T. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114500 · Cited by 55 · see citing works
Self-citationYuan, J., Ng, W. H., Lam, P. Y. P., Wang, Y., Xia, H., Yap, J., Guan, S. P., Lee, A. S. G., Wang, M., Baccarini, M., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0365-2 · Cited by 55 · see citing works
BRAF mutation leading to central nervous system rosai‐dorfman disease
Richardson, T. E., Wachsmann, M., Oliver, D., Abedin, Z. R., Ye, D., Burns, D. K., Raisanen, J. M., Greenberg, B. M., & Hatanpaa, K. J. (2018) · Annals of Neurology · doi:10.1002/ana.25281 · Cited by 54 · see citing works
The mechanism of Raf activation through dimerization
Zhang, M., Maloney, R., Jang, H., & Nussinov, R. (2021) · Chemical Science · doi:10.1039/d1sc03444h · Cited by 53 · see citing works
Kemps, P. G., Zondag, T. C. E., Arnardóttir, H. B., Solleveld‐Westerink, N., Borst, J., Steenwijk, E. C., van Egmond, D., Swennenhuis, J. F., Stelloo, E., Trambusti, I., et al. (2022) · Blood Advances · doi:10.1182/bloodadvances.2022007947 · Cited by 52 · see citing works
Current Advances in Thyroid Cancer Management. Are We Ready for the Epidemic Rise of Diagnoses?
Rusinek, D., Chmielik, E., Krajewska, J., Jarząb, M., Oczko‐Wojciechowska, M., Czarniecka, A., & Jarząb, B. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081817 · Cited by 48 · see citing works
Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Singh, H., Keller, R. B., Kapner, K. S., Dilly, J., Raghavan, S., Yuan, C., Cohen, E. F., Tolstorukov, M. Y., Andrews, E., Brais, L. K., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-3930 · Cited by 46 · see citing works
KRAS targeting antibody synergizes anti-cancer activity of gemcitabine against pancreatic cancer
Kang, Y. W., Lee, J. E., Jung, K. H., Son, M. K., Shin, S., Kim, S., Fang, Z., YAN, H. H., Park, J. H., Han, B., et al. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.09.013 · Cited by 46 · see citing works
Kattan, W. E., Liu, J., Montufar‐Solis, D., Hong, L., Barathi, B. B., van der Hoeven, R., Zhou, Y., & Hancock, J. F. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2114126118 · Cited by 46 · see citing works
Challenges and Opportunities in the Crusade of BRAF Inhibitors: From 2002 to 2022
Singh, A. K., Sonawane, P., Kumar, A., Singh, H., Naumovich, V., Pathak, P., Grishina, M., Khalilullah, H., Jaremko, M., Emwas, A.-H. M., et al. (2023) · ACS Omega · doi:10.1021/acsomega.3c00332 · Cited by 45 · see citing works
Yao, Y.-M., Donoho, G. P., Iversen, P. W., Zhang, Y., Horn, R. D. V., Forest, A., Novosiadly, R. D., Webster, Y., Ebert, P. J., Bray, S. M., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-3250 · Cited by 44 · see citing works
Self-citationSheikine, Y., Pavlick, D. C., Klempner, S. J., Trabucco, S. E., Chung, J., Rosenzweig, M. R., Wang, K., Velcheti, V., Frampton, G. M., Peled, N., et al. (2018) · JCO Precision Oncology · doi:10.1200/po.17.00172 · Cited by 44 · see citing works
Adamopoulos, C., Cave, D. D., & Papavassiliou, A. G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031631 · Cited by 41 · see citing works
Koujima, T., Tazawa, H., Ieda, T., Araki, H., Fushimi, T., Shoji, R., Kuroda, S., Kikuchi, S., Yoshida, R., Umeda, Y., et al. (2020) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2020.03.016 · Cited by 43 · see citing works
Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAFV600E-Mutant Human Glioma
Schreck, K. C., Morin, A., Zhao, G., Allen, A. N., Flannery, P., Glantz, M., Green, A. L., Jones, C., Jones, K. L., Kilburn, L. B., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-2660 · Cited by 41 · see citing works
Thomas, R. J., Wiley, C. A., Droste, E. L., Robertson, J. B., Inman, B. A., & Breen, M. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010575 · Cited by 40 · see citing works
Targeting CRAF kinase in anti-cancer therapy: progress and opportunities
Wang, P., Laster, K. V., Jia, X., Dong, Z., & Liu, K. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01903-x · Cited by 40 · see citing works
RIPK1 inhibitors: A key to unlocking the potential of necroptosis in drug development
Bai, Y., Qiao, Y., Li, M., Yang, W., Chen, H., Wu, Y., & Zhang, H. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116123 · Cited by 40 · see citing works
The role of CRAF in cancer progression: from molecular mechanisms to precision therapies
Riaud, M., Maxwell, J., Soria‐Bretones, I., Dankner, M., Li, M., & Rose, A. A. N. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-023-00650-x · Cited by 39 · see citing works
Cope, N. J., Novak, B., Liu, Z., Cavallo, M., Gunderwala, A. Y., Connolly, M., & Wang, Z. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011536 · Cited by 39 · see citing works
Weinberg, F., Griffin, R., Fröhlich, M., Heining, C., Braun, S. L., Spohr, C., Iconomou, M., Hollek, V., Röring, M., Horak, P., et al. (2019) · Oncogene · doi:10.1038/s41388-019-1021-1 · Cited by 38 · see citing works
Epigenetic Mechanisms of Escape from BRAF Oncogene Dependency
Khaliq, M., & Fallahi‐Sichani, M. (2019) · Cancers · doi:10.3390/cancers11101480 · Cited by 37 · see citing works
Tanaka, H. Y., Nakazawa, T., Enomoto, A., Masamune, A., & Kano, M. R. (2023) · Cancers · doi:10.3390/cancers15030724 · Cited by 40 · see citing works
BRAF internal deletions and resistance to BRAF / MEK inhibitor therapy
Johnson, D. B., Childress, M. A., Chalmers, Z. R., Frampton, G. M., Ali, S. M., Rubinstein, S. M., Fabrizio, D. A., Ross, J. S., Balasubramanian, S., Miller, V. A., et al. (2017) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12674 · Cited by 37 · see citing works
Drug resistance in targeted cancer therapies with RAF inhibitors
Degirmenci, U., Yap, J., Sim, Y. R. M., Qin, S., & Hu, J. (2021) · Cancer Drug Resistance · doi:10.20517/cdr.2021.36 · Cited by 36 · see citing works
Coordinating ERK signaling via the molecular scaffold Kinase Suppressor of Ras
Frodyma, D. E., Neilsen, B. K., Costanzo-Garvey, D. L., Fisher, K. W., & Lewis, R. E. (2017) · F1000Research · doi:10.12688/f1000research.11895.1 · Cited by 35 · see citing works
Pham, N., Radulovich, N., Ibrahimov, E., Martins-Filho, S. N., Li, Q., Pintilie, M., Weiss, J., Raghavan, V., Cabanero, M., Denroche, R. E., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-90049-1 · Cited by 32 · see citing works
Bilal, F., Arenas, E. J., Pedersen, K., Martínez-Sabadell, A., Nabet, B., Guruceaga, E., Vicent, S., Tabernero, J. M., Macarulla, T. M., & Arribas, J. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-4263 · Cited by 32 · see citing works
RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics
Kattan, W. E., & Hancock, J. F. (2020) · Biochemical Journal · doi:10.1042/bcj20190839 · Cited by 31 · see citing works
Rapid generation of drug-resistance alleles at endogenous loci using CRISPR-Cas9 indel mutagenesis
Ipsaro, J. J., Shen, C., Arai, E., Xu, Y., Kinney, J. B., Joshua‐Tor, L., Vakoc, C. R., & Shi, J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172177 · Cited by 31 · see citing works
Making NSCLC Crystal Clear: How Kinase Structures Revolutionized Lung Cancer Treatment
Vilachã, J. F., Mitchel, S. C., Akele, M. Z., Evans, S., & Groves, M. R. (2020) · Crystals · doi:10.3390/cryst10090725 · Cited by 29 · see citing works
Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution
Monberg, M. E., Geiger, H., Lee, J. J., Sharma, R., Semaan, A., Bernard, V., Wong, J., Wang, F., Liang, S., Swartzlander, D. B., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31376-3 · Cited by 30 · see citing works
Hendifar, A. E., Blais, E. M., Wolpin, B. M., Subbiah, V., Collisson, E. A., Singh, I., Cannon, T. L., Shaw, K. R. M., Petricoin, E. F., Klempner, S. J., et al. (2021) · JCO Precision Oncology · doi:10.1200/po.20.00494 · Cited by 31 · see citing works
Mechanism and inhibition of BRAF kinase
Gunderwala, A. Y., Cope, N. J., & Wang, Z. (2022) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2022.102205 · Cited by 29 · see citing works
Yaeger, R. D., McKean, M. A., Haq, R., Beck, J. T., Taylor, M. H., Cohen, J. E., Bowles, D. W., Gadgeel, S. M., Mihalcioiu, C. L. D., Papadopoulos, K. P., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0024 · Cited by 28 · see citing works
Lee, M. S., & Pant, S. (2021) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_321255 · Cited by 29 · see citing works
Pan, J., Zhou, H. K., Zhu, S.-B., Huang, J.-L., Zhao, X.-X., Ding, H., & Pan, Y.-L. (2018) · Cancer Management and Research · doi:10.2147/cmar.s170105 · Cited by 28 · see citing works
Mekkawy, A. I., Naguib, Y. W., Alhaj-Suliman, S. O., Wafa, E. I., Ebeid, K., Acri, T. M., & Salem, A. K. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120876 · Cited by 27 · see citing works
Weng, W., Meng, T., Pu, J., Ma, L., Shen, Y., Wang, Z., Pan, R., Wang, M., Chen, C., Wang, L., et al. (2023) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-23-0198 · Cited by 28 · see citing works
Wajapeyee, N., Parajuli, K. R., Chava, S., Pattanayak, R., Manna, D. L. D., Shrestha, D., Yang, E. S.-H., Cai, G., Johnson, D. B., & Gupta, R. (2020) · Oncogenesis · doi:10.1038/s41389-020-0228-x · Cited by 27 · see citing works
New Targets in Non–Small Cell Lung Cancer
Park, S. J., More, S., Murtuza, A., Woodward, B. D., & Husain, H. (2016) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2016.08.010 · Cited by 26 · see citing works
BRAF-Driven Pancreatic Cancer: Prevalence, Molecular Features, and Therapeutic Opportunities
Ciner, A., Jiang, Y., & Hausner, P. F. (2022) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-22-0626 · Cited by 25 · see citing works
Current Insights into the Role of BRAF Inhibitors in Treatment of Melanoma
Kumar, P., Singh, A. K., Kumar, A., & Thareja, S. (2022) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520622666220624164152 · Cited by 24 · see citing works
Disrupted molecular glue complex drives RAS inhibitor resistance
Sang, B., Ye, L. F., Fu, Z., Pourfarjam, Y., Cuevas-Navarro, A., Fan, S., Hu, F., Washington, A., Rodriguez, D. J., Vides, A., et al. (2026) · Cell · doi:10.1016/j.cell.2026.03.031 · Cited by 42 · see citing works
Genomic profile of columnar cell variant of papillary thyroid carcinoma
Janovitz, T., Williamson, D. F. K., Wong, K. S., Dong, F., & Barletta, J. A. (2021) · Histopathology · doi:10.1111/his.14374 · Cited by 23 · see citing works
Desai, A., Menon, S. P., & Dy, G. K. (2016) · PubMed Central · doi:10.28092/j.issn.2095-3941.2016.0008 · Cited by 22 · see citing works
Yap, J., Deepak, R. N. V. K., Tian, Z., Ng, W. H., Goh, K. C., Foo, A., Tee, Z. H., Mohanam, M. P., Sim, Y. R. M., Degirmenci, U., et al. (2021) · Science Advances · doi:10.1126/sciadv.abg0390 · Cited by 21 · see citing works
Signaling pathways, microenvironment, and targeted treatments in Langerhans cell histiocytosis
Gao, X., Li, J., & Cao, X. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-022-00917-0 · Cited by 21 · see citing works
Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2
Chen, W., & Park, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914837 · Cited by 20 · see citing works
Li, J., Liu, W., Mojumdar, K., Kim, H., Zhou, Z., Ju, Z., Kumar, S. V., Ng, P. K., Chen, H., Davies, M. A., et al. (2024) · Nature Cancer · doi:10.1038/s43018-024-00817-x · Cited by 21 · see citing works
Gampa, G., Kim, M., Mohammad, A., Parrish, K. E., Mladek, A., Sarkaria, J., & Elmquist, W. (2019) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.253708 · Cited by 21 · see citing works
Anti‐angiogenic effects of the blue‐green alga Arthrospira platensis on pancreatic cancer
Markova, I., Koníčková, R., Vaňková, K., Leníček, M., Kolář, M., Strnad, H., Hradilová, M., Šáchová, J., Rasl, J., Klímová, Z., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14922 · Cited by 19 · see citing works
Khoury, J. D., Tashakori, M., Yang, H. Y., Loghavi, S., Wang, Y., Wang, J., Piya, S., & Borthakur, G. M. (2020) · Cancers · doi:10.3390/cancers12123511 · Cited by 19 · see citing works
Diehl, J. N., Hibshman, P. S., Ozkan‐Dagliyan, I., Goodwin, C. M., Howard, S. V., Cox, A. D., & Der, C. J. (2022) · Advances in cancer research · doi:10.1016/bs.acr.2021.07.008 · Cited by 18 · see citing works
Targeting RAF dimers in RAS mutant tumors: From biology to clinic
Yin, H., Tang, Q., Xia, H., & Bi, F. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.02.018 · Cited by 18 · see citing works
Rational design, synthesis, and biological evaluation of Pan-Raf inhibitors to overcome resistance
Wang, L., Zhu, G., Zhang, Q., Duan, C., Zhang, Y., Zhang, Z., Zhou, Y., Lu, T., & Tang, W. (2017) · Organic & Biomolecular Chemistry · doi:10.1039/c7ob00518k · Cited by 18 · see citing works
Self-citationThe Evolution of BRAF Activation in Non-Small-Cell Lung Cancer
Zhang, L., Zheng, L., Yang, Q., & Sun, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.882940 · Cited by 18 · see citing works
Rohrer, L., Spohr, C., Beha, C., Griffin, R., Braun, S. L., Halbach, S., & Brummer, T. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01146-9 · Cited by 17 · see citing works
Lauinger, M., Christen, D., Klar, R. F. U., Roubaty, C., Heilig, C. E., Stumpe, M., Knox, J. J., Radulovich, N., Tamblyn, L., Xie, I. Y., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade7486 · Cited by 17 · see citing works
RAF and MEK Inhibitors in Non-Small Cell Lung Cancer
Adamopoulos, C., Papavassiliou, K. A., Poulikakos, P. I., & Papavassiliou, A. G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094633 · Cited by 17 · see citing works
Pratt, D. W., Camelo-Piragua, S. I., McFadden, K. A., Leung, D., Mody, R. J., Chinnaiyan, A. M., Koschmann, C. J., & Venneti, S. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0525-1 · Cited by 17 · see citing works
- Authors
- Chen, S.-H., Zhang, Y., Van Horn, R. D., Yin, T., Buchanan, S., Yadav, V., Mochalkin, I., Wong, S. S., Yue, Y. G., Huber, L., Conti, I., Henry, J. R., Starling, J. J., Plowman, G. D., & Peng, S.-B.
- Affiliations
- Eli Lilly (United States) (US)
- 1Oncology Research, Eli Lilly and Company, Indianapolis, Indiana.
- Corresponding author
- Peng, Sheng-Bin
- ORCID
- Venue
- Cancer Discovery
- Published
- 2016-03-01
- Volume
- 6
- Issue
- 3
- Pages
- 300-315
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2309935793
- Cited by
- 171
- References
- 47
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 24 · 2023: 22 · 2022: 23 · 2021: 15 · 2020: 13 · 2019: 16 · 2018: 17 · 2017: 19 · 2016: 5
- FWCI
- 9.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- LY3009120, vemurafenib resistance, αC-helix, MAPK signaling, KRAS wild-type pancreatic cancer, proximity ligation assay
- MeSH terms
- Ectopic Gene Expression, Animals, Antineoplastic Agents, Cell Transformation, Neoplastic, Disease Models, Animal, Humans, Models, Molecular, Phenylurea Compounds, Protein Conformation, Pyrimidines, Gene Expression, Gene Deletion, Drug Resistance, Neoplasm, MAP Kinase Signaling System, Xenograft Model Antitumor Assays, Cell Line, Tumor, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf, Mice, Protein Interaction Domains and Motifs, Protein Multimerization
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