Cited by 409Melanoma and MAPK PathwaysProtein Kinase Regulation and GTPase SignalingProtein Tyrosine Phosphatases

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New perspectives for targeting RAF kinase in human cancer

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Karoulia, Zoi, Gavathiotis, Evripidis, Poulikakos, Poulikos I.·2017·Nature Reviews Cancer

DOI 10.1038/nrc.2017.79PMC PMC6000833

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Abstract

The discovery that a subset of human tumours is dependent on mutationally deregulated BRAF kinase intensified the development of RAF inhibitors to be used as potential therapeutics. The US Food and Drug Administration (FDA)-approved second-generation RAF inhibitors vemurafenib and dabrafenib have elicited remarkable responses and improved survival of patients with BRAF-V600E/K melanoma, but their effectiveness is limited by resistance. Beyond melanoma, current clinical RAF inhibitors show modest efficacy when used for colorectal and thyroid BRAF-V600E tumours or for tumours harbouring BRAF alterations other than the V600 mutation. Accumulated experimental and clinical evidence indicates that the complex biochemical mechanisms of RAF kinase signalling account both for the effectiveness of RAF inhibitors and for the various mechanisms of tumour resistance to them. Recently, a number of next-generation RAF inhibitors, with diverse structural and biochemical properties, have entered preclinical and clinical development. In this Review, we discuss the current understanding of RAF kinase regulation, mechanisms of inhibitor action and related clinical resistance to these drugs. The recent elucidation of critical structural and biochemical aspects of RAF inhibitor action, combined with the availability of a number of structurally diverse RAF inhibitors currently in preclinical and clinical development, will enable the design of more effective RAF inhibitors and RAF-inhibitor-based therapeutic strategies, tailored to different clinical contexts.

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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Sorafenib in advanced hepatocellular carcinoma
Llovet, J. M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.-F., de Oliveira, A. C., Santoro, A., Raoul, J.-L., Forner, A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708857 · Cited by 13,097
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
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
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
A New Era of Systemic Therapy for Hepatocellular Carcinoma with Regorafenib and Lenvatinib
Kudo, M. (2017) · Liver Cancer · doi:10.1159/000462153 · Cited by 5,974
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Sorafenib in Advanced Hepatocellular Carcinoma
정, 재. (2008) · Cited by 5,586
Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma
Escudier, B. J., Eisen, T. G., Stadler, W. M., Szczylik, C. A., Oudard, S. M., Siebels, M., Négrier, S., Chevreau, C., Solska, E., Desai, A. A., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa060655 · Cited by 4,802
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.065 · Cited by 3,448
Genomic classification of cutaneous melanoma
Akbani, R., Akdemir, K. C., Aksoy, B. A., Albert, M., Ally, A., Amin, S. B., Arachchi, H., Arora, A., Auman, J. T., Ayala, B., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.044 · Cited by 3,151
Inhibition of Mutated, Activated BRAF in Metastatic Melanoma
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
Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
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 3,050
MAP kinase signalling pathways in cancer
Dhillon, A. S., Hagan, S., Rath, O., & Kolch, W. (2007) · Oncogene · doi:10.1038/sj.onc.1210421 · Cited by 2,995
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 2,863
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
Roberts, P. J., & Der, C. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210422 · Cited by 2,788
Targeting cancer with small molecule kinase inhibitors
Zhang, J., Yang, P. L., & Gray, N. S. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2559 · Cited by 2,648
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
Combined Vemurafenib and Cobimetinib in BRAF -Mutated Melanoma
Larkin, J., Ascierto, P. A., Dréno, B., Atkinson, V. G., Liszkay, G., Maio, M., Mandalà, M., Демидов, Л. В., Stroyakovskiy, D., Thomas, L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408868 · Cited by 2,115
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
Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma
Long, G. V., Stroyakovskiy, D., Gogas, H. J., Levchenko, E., de Braud, F., Larkin, J., Garbe, C., Jouary, T., Hauschild, A., Grob, J., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406037 · Cited by 1,969
Mammalian Ras interacts directly with the serine/threonine kinase raf
Vojtek, A. B., Hollenberg, S. M., & Cooper, J. A. (1993) · Cell · doi:10.1016/0092-8674(93)90307-c · Cited by 1,934
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
RAF 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 1,841
Self-citation
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
Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations
Hyman, D. M., Puzanov, I., Subbiah, V., Faris, J. E., Chau, I., Blay, J.-Y., Wolf, J., Raje, N. S., Diamond, E. L., Hollebecque, A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1502309 · Cited by 1,764
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 1,649
High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.
Kimura, E. T., Nikiforova, M. N., Zhu, Z., Knauf, J. A., Nikiforov, Y. E., & Fagin, J. A. (2003) · PubMed · Cited by 1,510
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 1,497
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
Self-citation
Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
Tsai, J., Lee, J. T., Wang, W., Zhang, J., Cho, H., Mamo, S., Bremer, R., Gillette, S., Kong, J., Haass, N. K., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711741105 · Cited by 1,346
BRAF mutation predicts sensitivity to MEK inhibition
Solit, D. B., Garraway, L. A., Pratilas, C. A., Sawai, A., Getz, G. A., Basso, A., Ye, Q., Lobo, J. M., She, Y., Osman, I., et al. (2005) · Nature · doi:10.1038/nature04304 · Cited by 1,326
Acquired Resistance to BRAF Inhibitors Mediated by a RAF Kinase Switch in Melanoma Can Be Overcome by Cotargeting MEK and IGF-1R/PI3K
Villanueva, J., Vultur, A., Lee, J. T., Somasundaram, R., Fukunaga‐Kalabis, M., Cipolla, A. K., Wubbenhorst, B. S., Xu, X., Gimotty, P. A., Kee, D., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.023 · Cited by 1,289
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 1,244
RAF/RAS oncogenes and mismatch-repair status
Rajagopalan, H., Bardelli, A., Lengauer, C., Kinzler, K. W., Vogelstein, B., & Velculescu, V. E. (2002) · Nature · doi:10.1038/418934a · Cited by 1,224
The RAF proteins take centre stage
Wellbrock, C., Karasarides, M., & Marais, R. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1498 · Cited by 1,223
Targeting RAS–ERK signalling in cancer: promises and challenges
Samatar, A. A., & Poulikakos, P. I. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4281 · Cited by 1,163
Self-citation
Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors
Wilson, T. R., Fridlyand, J., Yan, Y., Penuel, E., Burton, L., Chan, E., Peng, J., Lin, E., Wang, Y., Sosman, J., et al. (2012) · Nature · doi:10.1038/nature11249 · Cited by 1,134
RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors
Su, F., Virós, A., Milagre, C. S., Trunzer, K., Bollag, G. E., Spleiss, O., Reis-Filho, J. S., Kong, X., Koya, R. C., Flaherty, K. T., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1105358 · Cited by 1,056
BRAF Mutations in Hairy-Cell Leukemia
Tiacci, E., Trifonov, V. A., Schiavoni, G., Holmes, A. B., Kern, W., Martelli, M. P., Pucciarini, A., Bigerna, B., Pacini, R., Wells, V. A., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1014209 · Cited by 1,029
Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling
Wagle, N., Emery, C., Berger, M. F., Davis, M. J., Sawyer, A. M., Pochanard, P., Kehoe, S. M., Johannessen, C. M., MacConaill, L. E., Hahn, W. C., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.2312 · Cited by 1,028
EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF -Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib
Corcoran, R. B., Ebi, H., Turke, A. B., Coffee, E. M., Nishino, M., Cogdill, A. P., Brown, R. D., Della Pelle, P., Dias-Santagata, D., Hung, K. E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0341 · Cited by 1,022
Acquired Resistance and Clonal Evolution in Melanoma during BRAF Inhibitor Therapy
Shi, H., Hugo, W., Kong, X., Hong, A., Koya, R. C., Moriceau, G., Chodon, T., Guo, R., Johnson, D. B., Dahlman, K. B., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0642 · Cited by 982
Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study
McArthur, G. A., Chapman, P. B., Robert, C., Larkin, J., Haanen, J. B., Dummer, R., Ribas, A., Hogg, D., Hamid, O., Ascierto, P. A., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70012-9 · Cited by 977
Complexes of Ras⋅GTP with Raf-1 and Mitogen-Activated Protein Kinase Kinase
Moodie, S. A., Willumsen, B. M., Weber, M. J., & Wolfman, A. (1993) · Science · doi:10.1126/science.8503013 · Cited by 968
Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial
Falchook, G. S., Long, G. V., Kurzrock, R., Kim, K. B., Arkenau, H., Brown, M. P., Hamid, O., Infante, J. R., Millward, M., Pavlick, A. C., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60398-5 · Cited by 954
Tandem Duplication Producing a Novel Oncogenic BRAF Fusion Gene Defines the Majority of Pilocytic Astrocytomas
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 951
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 850
Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro
Warne, P. H., Vician, P. R., & Downward, J. (1993) · Nature · doi:10.1038/364352a0 · Cited by 729
Regulation of RAF protein kinases in ERK signalling
Lavoie, H., & Therrien, M. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3979 · Cited by 702
Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF -Mutated Colorectal Cancer
Kopetz, S., Desai, J., Chan, E., Hecht, J. R., O'Dwyer, P. J., Maru, D., Morris, V., Janku, F., Dasari, A., Chung, W., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.63.2497 · Cited by 697
Melanoma whole-exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance
Shi, H., Moriceau, G., Kong, X., Lee, M., Lee, H., Koya, R. C., Ng, C., Chodon, T., Scolyer, R. A., Dahlman, K. B., et al. (2012) · Nature Communications · doi:10.1038/ncomms1727 · Cited by 660
MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road
Caunt, C. J., Sale, M. J., Smith, P. D., & Cook, S. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4000 · Cited by 606
Development of immuno-oncology drugs — from CTLA4 to PD1 to the next generations
Hoos, A. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.35 · Cited by 601
Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas
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
Self-citation
Tumours 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
BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition
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
Self-citation
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 505
Therapy-induced tumour secretomes promote resistance and tumour progression
Obenauf, A. C., Zou, Y., Ji, A. L., Vanharanta, S., Shu, W., Shi, H., Kong, X., Bosenberg, M., Wiesner, T., Rosen, N. X., et al. (2015) · Nature · doi:10.1038/nature14336 · Cited by 503
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
The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner
Joseph, E. W., Pratilas, C. A., Poulikakos, P. I., Tadi, M., Wang, W., Taylor, B. S., Halilovic, E., Persaud, Y., Xing, F., Viale, A. J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008990107 · Cited by 446
Self-citation
Wild-Type and Mutant B-RAF Activate C-RAF through Distinct Mechanisms Involving Heterodimerization
Garnett, M. J., Rana, S., Paterson, H., Barford, D., & Marais, R. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.10.022 · Cited by 416
Regulation and Role of Raf-1/B-Raf Heterodimerization
Rushworth, L. K., Hindley, A. D., O’Neill, E. E., & Kölch, W. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.6.2262-2272.2006 · Cited by 415
Discovery of a novel Raf kinase inhibitor.
Lyons, J. F., Wilhelm, S. M., Hibner, B., & Bollag, G. E. (2001) · Endocrine Related Cancer · doi:10.1677/erc.0.0080219 · Cited by 410
RG7204 (PLX4032), a Selective BRAFV600E Inhibitor, Displays Potent Antitumor Activity in Preclinical Melanoma Models
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 404
Raf Family Kinases: Old Dogs Have Learned New Tricks
Matallanas, D., Birtwistle, M. R., Romano, D., Zebisch, A., Rauch, J., von Kriegsheim, A., & Kölch, W. (2011) · Genes & Cancer · doi:10.1177/1947601911407323 · Cited by 401
Inhibition of Ras for Cancer Treatment: The Search Continues
Baines, A. T., Xu, D., & Der, C. J. (2011) · Future Medicinal Chemistry · doi:10.4155/fmc.11.121 · Cited by 401
RAF inhibitors that evade paradoxical MAPK pathway activation
Zhang, C., Spevak, W. R., Zhang, Y., Burton, E. A., Ma, Y., Habets, G. G. M., Zhang, J., Lin, J. Y.-S., Ewing, T. J. A., Matusow, B., et al. (2015) · Nature · doi:10.1038/nature14982 · Cited by 396
Ras Activation of the Raf Kinase: Tyrosine Kinase Recruitment of the MAP Kinase Cascade
Avruch, J. (2001) · Recent Progress in Hormone Research · doi:10.1210/rp.56.1.127 · Cited by 395
Relief of Feedback Inhibition of HER3 Transcription by RAF and MEK Inhibitors Attenuates Their Antitumor Effects in BRAF -Mutant Thyroid Carcinomas
Montero-Conde, C., Ruiz-Llorente, S., Dominguez, J. M., Knauf, J. A., Viale, A., Sherman, E. J., Ryder, M., Ghossein, R. A., Rosen, N., & Fagin, J. A. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0531 · Cited by 382
Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma
Long, G. V., Fung, C., Menzies, A. M., Pupo, G. M., Carlino, M. S., Hyman, J., Shahheydari, H., Tembe, V., Thompson, J. F., Saw, R. P., et al. (2014) · Nature Communications · doi:10.1038/ncomms6694 · Cited by 375
The distribution of BRAF gene fusions in solid tumors and response to targeted therapy
Ross, J. S., Wang, K., Chmielecki, J., Gay, L. M., Johnson, A., Chudnovsky, J., Yelensky, R., Lipson, D., Ali, S. M., Elvin, J. A., et al. (2015) · International Journal of Cancer · doi:10.1002/ijc.29825 · Cited by 354
Tunable-Combinatorial Mechanisms of Acquired Resistance Limit the Efficacy of BRAF/MEK Cotargeting but Result in Melanoma Drug Addiction
Moriceau, G., Hugo, W., Hong, A., Shi, H., Kong, X., Yu, C. C., Koya, R. C., Samatar, A. A., Khanlou, N., Braun, J. G., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.11.018 · Cited by 351
PLX4032, a selective BRAF V600E kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF WT melanoma cells
Halaban, R., Zhang, W., Bacchiocchi, A., Cheng, E., Parisi, F., Ariyan, S., Krauthammer, M. O., McCusker, J. P., Kluger, Y., & Sznol, M. (2010) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2010.00685.x · Cited by 325
Active Ras induces heterodimerization of cRaf and BRaf.
Weber, C., Slupsky, J. R., Kalmes, H. A., & Rapp, U. R. (2001) · PubMed · Cited by 312
Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers
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 303
Allosteric Activation of Functionally Asymmetric RAF Kinase Dimers
Hu, J., Stites, E. C., Yu, H., Germino, E., Meharena, H. S., Stork, P. A., Kornev, A. P., Taylor, S. S., & Shaw, A. S. (2013) · Cell · doi:10.1016/j.cell.2013.07.046 · Cited by 303
Inhibitor hijacking of Akt activation
Okuzumi, T., Fiedler, D., Zhang, C., Gray, D. C., Aizenstein, B., Hoffman, R., & Shokat, K. M. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.183 · Cited by 302
Dynamics-Driven Allostery in Protein Kinases
Kornev, A. P., & Taylor, S. S. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.09.002 · Cited by 289
Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas
Sievert, A. J., Lang, S., Boucher, K. L., Madsen, P. J., Slaunwhite, E., Choudhari, N., Kellet, M., Storm, P. B., & Resnick, A. C. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219232110 · Cited by 285
Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1)
Pearce, L. R., Alton, G., Richter, D. T., Kath, J. C., Lingardo, L., Chapman, J., Hwang, C., & Alessi, D. R. (2010) · Biochemical Journal · doi:10.1042/bj20101024 · Cited by 273
Paradoxical activation of Raf by a novel Raf inhibitor
Hall-Jackson, C. A., Eyers, P. A., Cohen, P., Goedert, M., Boyle, F. T., Hewitt, N., Plant, H., & Hedge, P. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)80088-x · Cited by 264
Demonstration of a Genetic Therapeutic Index for Tumors Expressing Oncogenic BRAF by the Kinase Inhibitor SB-590885
King, A. J., Patrick, D. R., Batorsky, R. S., Ho, M. L., Hiếu, T., Zhang, S. Y., Kumar, R., Rusnak, D. W., Takle, A. K., Wilson, D. M., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-2554 · Cited by 257
Mutant BRAF Melanomas—Dependence and Resistance
Poulikakos, P. I., & Rosen, N. X. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.01.008 · Cited by 256
Self-citation
Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling
Haling, J. R., Sudhamsu, J., Yen, I., Sideris, S., Sandoval, W. N., Phung, W., Bravo, B. J., Giannetti, A. M., Peck, A., Masselot, A., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.07.007 · Cited by 242
Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2
Foster, S. A., Whalen, D. M., Özen, A., Wongchenko, M. J., Yin, J., Yen, I., Schaefer, G., Mayfield, J. D., Chmielecki, J., Stephens, P. J., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.02.010 · Cited by 217
Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma
Girotti, M. R., Lopes, F., Preece, N., Niculescu-Duvaz, D., Zambon, A., Davies, L., Whittaker, S., Saturno, G., Viros, A., Pedersen, M., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.11.006 · Cited by 212
Chapter 1 Ras Signaling and Therapies
Young, A. E., Lyons, J., Miller, A. L., Phan, V. T., Alarcón, I. R., & McCormick, F. P. (2009) · Advances in cancer research · doi:10.1016/s0065-230x(09)02001-6 · Cited by 211
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 211
An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling
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 205
Self-citation
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Villanueva, J., Infante, J. R., Krepler, C., Reyes-Uribe, P. I., Samanta, M., Chen, H., Li, B., Swoboda, R., Wilson, M. A., Vultur, A., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.08.023 · Cited by 200
Autoregulation of the Raf-1 serine/threonine kinase
Cutler, R. E., Stephens, R. M., Saracino, M. R., & Morrison, D. K. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9214 · Cited by 200
BRAF L597 Mutations in Melanoma Are Associated with Sensitivity to MEK Inhibitors
Dahlman, K. B., Xia, J., Hutchinson, K. E., Ng, C., Hucks, D., Jia, P., Atefi, M. S., Su, Z., Branch, S., Lyle, P. L., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0097 · Cited by 196
Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization
Lavoie, H., Thevakumaran, N., Gavory, G., Li, J. J., Padeganeh, A., Guiral, S., Duchaine, J., Mao, D. Y. L., Bouvier, M., Sicheri, F., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1257 · Cited by 181
Antitumor Efficacy of the Novel RAF Inhibitor GDC-0879 Is Predicted by BRAFV600E Mutational Status and Sustained Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway Suppression
Hoeflich, K. P., Herter, S., Tien, J., Wong, L. L.-Y., Berry, L., Chan, J., O'Brien, C. L., Modrusan, Z. D., Seshagiri, S., Lackner, M. R., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3563 · Cited by 173
Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120
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., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0896 · Cited by 171
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Thevakumaran, N., Lavoie, H., Critton, D., Tebben, A. J., Marinier, A., Sicheri, F., & Therrien, M. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2924 · Cited by 169
Distinct requirement for an intact dimer interface in wild‐type, V600E and kinase‐dead B‐Raf signalling
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
PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity
Cameron, A. J. M., Escribano, C., Saurin, A. T., Kostelecky, B., & Parker, P. J. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1606 · Cited by 136
Modulation of Activation-Loop Phosphorylation by JAK Inhibitors Is Binding Mode Dependent
Andraos, R., Qian, Z., Bonenfant, D., Rubert, J., Vangrevelinghe, E., Scheufler, C., Marque, F., Régnier, C. H., Pover, A. D., Ryckelynck, H., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0324 · Cited by 135
RAF Inhibitors Activate the MAPK Pathway by Relieving Inhibitory Autophosphorylation
Holderfield, M. T., Merritt, H., Chan, J., Wallroth, M., Tandeske, L., Zhai, H., Tellew, J. E., Hardy, S. F., Hekmat-Nejad, M., Stuart, D. D., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.03.033 · Cited by 129
Mechanism and consequences of RAF kinase activation by small-molecule inhibitors
Holderfield, M. T., Nagel, T., & Stuart, D. D. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.139 · Cited by 128
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Nakamura, A., Arita, T., Tsuchiya, S., Donelan, J., Chouitar, J., Carideo, E. G., Galvin, K. M., Okaniwa, M., Ishikawa, T., & Yoshida, S. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1825 · Cited by 124
A Braf kinase-inactive mutant induces lung adenocarcinoma
Nieto, P., Ambrogio, C., Esteban-Burgos, L., Goméz-López, G., Blasco, M. T., Yao, Z., Marais, R., Rosen, N. X., Chiarle, R., Pisano, D. G., et al. (2017) · Nature · doi:10.1038/nature23297 · Cited by 122
Differential activity of MEK and ERK inhibitors in BRAF inhibitor resistant melanoma
Carlino, M. S., Todd, J. R., Gowrishankar, K., Mijatov, B., Pupo, G. M., Fung, C., Snoyman, S., Hersey, P., Long, G. V., Kefford, R. F., et al. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.01.003 · Cited by 120
BRAF inhibitor activity in V600R metastatic melanoma
Klein, O., Clements, A., Menzies, A. M., O'Toole, S. A., Kefford, R. F., & Long, G. V. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.11.004 · Cited by 114
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Okaniwa, M., Hirose, M., Arita, T., Yabuki, M., Nakamura, A., Takagi, T., Kawamoto, T., Uchiyama, N., Sumita, A., Tsutsumi, S., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400778d · Cited by 112
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Sun, Y., Alberta, J. A., Pilarz, C., Calligaris, D., Chadwick, E. J., Ramkissoon, S. H., Ramkissoon, L. A., Matía, V., Mazzola, E., Goumnerova, L. C., et al. (2016) · Neuro-Oncology · doi:10.1093/neuonc/now261 · Cited by 107
Clinical detection and categorization of uncommon and concomitant mutations involving BRAF
Zheng, G., Tseng, L., Chen, G., Haley, L. M., Illei, P. B., Gocke, C. D., Eshleman, J. R., & Lin, M. (2015) · BMC Cancer · doi:10.1186/s12885-015-1811-y · Cited by 105
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Waizenegger, I. C., Baum, A., Steurer, S., Stadtmüller, H., Bader, G., Schaaf, O., Garin‐Chesa, P., Schlattl, A., Schweifer, N., Haslinger, C., et al. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0617 · Cited by 101
The c‐Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK‐ERK and Akt‐independent mechanism
Chin, P. C., Liu, L., Morrison, B. E., Siddiq, A., Ratan, R. R., Bottiglieri, T., & D’Mello, S. R. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02530.x · Cited by 93
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BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF -Mutated Colorectal Cancers
Tang, Z., Yuan, X., Du, R., Cheung, S.-H., Zhang, G., Wei, J., Zhao, Y., Feng, Y., Peng, H., Zhang, Y., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0262 · Cited by 82
Antiproliferative Effects of Continued Mitogen-Activated Protein Kinase Pathway Inhibition following Acquired Resistance to BRAF and/or MEK Inhibition in Melanoma
Carlino, M. S., Gowrishankar, K., Saunders, C. A. B., Pupo, G. M., Snoyman, S., Zhang, X. D., Saw, R. P. M., Becker, T. M., Kefford, R. F., Long, G. V., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0011 · Cited by 82
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Le, K., Blomain, E. S., Rodeck, U., & Aplin, A. E. (2013) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12092 · Cited by 72
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Basile, K. J., Le, K., Hartsough, E. J., & Aplin, A. E. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12218 · Cited by 53
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Shelton, J. G., Moye, P. W., Steelman, L. S., Blalock, W. L., Lee, J. T., Franklin, R. A., McMahon, M., & McCubrey, J. A. (2003) · Leukemia · doi:10.1038/sj.leu.2403052 · Cited by 49
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Authors: Karoulia, Z., Gavathiotis, E., & Poulikakos, P. I.
Affiliations: Tisch Cancer Institute (US)
Albert Einstein College of Medicine (US)
Corresponding author: Poulikakos, Poulikos I.
ORCID: Karoulia, Zoi
Gavathiotis, Evripidis
Poulikakos, Poulikos I.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2017-10-06
Volume: 17
Issue: 11
Pages: 676-691
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc.2017.79
PMC: PMC6000833
OpenAlex: W2762842128
Cited by: 404
References: 125
Citations by year: 2026: 24 · 2025: 37 · 2024: 48 · 2023: 48 · 2022: 46 · 2021: 52 · 2020: 51 · 2019: 58 · 2018: 37 · 2017: 2
FWCI: 3.83
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Dermatology Foundation
Melanoma Research Alliance
Sidney Kimmel Foundation for Cancer Research
Sidney Kimmel Foundation
Pershing Square Sohn Cancer Research Alliance
National Institutes of Health
National Cancer Institute (R01CA178394, R01CA204314)
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: Raf kinase, BRAF mutation, RAF inhibitors, vemurafenib, dabrafenib, melanoma, BRAF V600E mutation, drug resistance, colorectal cancer, thyroid cancer, inhibitor design
MeSH terms: Humans, Neoplasms, Protein Kinase Inhibitors, raf Kinases

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New perspectives for targeting RAF kinase in human cancer

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