Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma

被引:141
作者
Fedorenko, Inna V. [1 ,2 ]
Paraiso, Kim H. T. [1 ,2 ]
Smalley, Keiran S. M. [1 ,2 ]
机构
[1] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Program Mol Oncol, Tampa, FL 33612 USA
[2] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Comprehens Melanoma Res Ctr, Tampa, FL 33612 USA
关键词
BRAF; Melanoma; Vemurafenib; MEK; Resistance; Cot; MAPK; HEDGEHOG PATHWAY INHIBITOR; SIGNALING PATHWAY; MEDIATES RESISTANCE; ANTITUMOR-ACTIVITY; KINASE INHIBITOR; RAF INHIBITOR; CELL-LINES; PHASE-II; MUTATIONS; CANCER;
D O I
10.1016/j.bcp.2011.05.015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The discovery of activating BRAF V600E mutations in 50% of all cutaneous melanomas has revolutionized the understanding of melanoma biology and provided new strategies for the therapeutic management of this deadly disease. Highly potent small molecule inhibitors of BRAF are now showing great promise as a novel therapeutic strategy for melanomas harboring activating BRAF V600E mutations and are associated with high levels of response. This commentary article discusses the latest data on the role of mutated BRAF in the development and progression of melanoma as the basis for understanding the mechanism of action of BRAF inhibitors in the preclinical and clinical settings. We further address the issue of BRAF inhibitor resistance and outline the latest insights into the mechanisms of therapeutic escape as well as describing approaches to prevent and abrogate the onset of both intrinsic and acquired drug resistance. It is likely that our evolving understanding of melanoma genetics and signaling will allow for the further personalization of melanoma therapy with the goal of improving clinical responses. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:201 / 209
页数:9
相关论文
共 77 条
[1]   Oncogenic BRAF Induces Melanoma Cell Invasion by Downregulating the cGMP-Specific Phosphodiesterase PDE5A [J].
Arozarena, Imanol ;
Sanchez-Laorden, Berta ;
Packer, Leisl ;
Hidalgo-Carcedo, Cristina ;
Hayward, Robert ;
Viros, Amaya ;
Sahai, Erik ;
Marais, Richard .
CANCER CELL, 2011, 19 (01) :45-57
[2]   KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway [J].
Bauer, S. ;
Duensing, A. ;
Demetri, G. D. ;
Fletcher, J. A. .
ONCOGENE, 2007, 26 (54) :7560-7568
[3]   Mutant B-RAF mediates resistance to anoikis via Bad and Bim [J].
Boisvert-Adamo, K. ;
Aplin, A. E. .
ONCOGENE, 2008, 27 (23) :3301-3312
[4]   Mcl-1 Is Required for Melanoma Cell Resistance to Anoikis [J].
Boisvert-Adamo, Karen ;
Longmate, Whitney ;
Abel, Ethan V. ;
Aplin, Andrew E. .
MOLECULAR CANCER RESEARCH, 2009, 7 (04) :549-556
[5]   Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma [J].
Bollag, Gideon ;
Hirth, Peter ;
Tsai, James ;
Zhang, Jiazhong ;
Ibrahim, Prabha N. ;
Cho, Hanna ;
Spevak, Wayne ;
Zhang, Chao ;
Zhang, Ying ;
Habets, Gaston ;
Burton, ElizabethA. ;
Wong, Bernice ;
Tsang, Garson ;
West, Brian L. ;
Powell, Ben ;
Shellooe, Rafe ;
Marimuthu, Adhirai ;
Nguyen, Hoa ;
Zhang, Kam Y. J. ;
Artis, Dean R. ;
Schlessinger, Joseph ;
Su, Fei ;
Higgins, Brian ;
Iyer, Raman ;
D'Andrea, Kurt ;
Koehler, Astrid ;
Stumm, Michael ;
Lin, Paul S. ;
Lee, Richard J. ;
Grippo, Joseph ;
Puzanov, Igor ;
Kim, Kevin B. ;
Ribas, Antoni ;
McArthur, Grant A. ;
Sosman, Jeffrey A. ;
Chapman, Paul B. ;
Flaherty, Keith T. ;
Xu, Xiaowei ;
Nathanson, Katherine L. ;
Nolop, Keith .
NATURE, 2010, 467 (7315) :596-599
[6]   Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function [J].
Boni, Andrea ;
Cogdill, Alexandria P. ;
Dang, Ping ;
Udayakumar, Durga ;
Njauw, Ching-Ni Jenny ;
Sloss, Callum M. ;
Ferrone, Cristina R. ;
Flaherty, Keith T. ;
Lawrence, Donald P. ;
Fisher, David E. ;
Tsao, Hensin ;
Wargo, Jennifer A. .
CANCER RESEARCH, 2010, 70 (13) :5213-5219
[7]   Oncogenic BRAFV600E inhibits BIM expression to promote melanoma cell survival [J].
Cartlidge, Robert A. ;
Thomas, G. R. ;
Cagnol, Sebastien ;
Jong, Kimberly A. ;
Molton, Sarah A. ;
Finch, Andrew J. ;
McMahon, Martin .
PIGMENT CELL & MELANOMA RESEARCH, 2008, 21 (05) :534-544
[8]   BRAF Gene Amplification Can Promote Acquired Resistance to MEK Inhibitors in Cancer Cells Harboring the BRAF V600E Mutation [J].
Corcoran, Ryan B. ;
Dias-Santagata, Dora ;
Bergethon, Kristin ;
Iafrate, A. John ;
Settleman, Jeffrey ;
Engelman, Jeffrey A. .
SCIENCE SIGNALING, 2010, 3 (149)
[9]  
Dankort D., 2009, Nat Genet
[10]   Mutations of the BRAF gene in human cancer [J].
Davies, H ;
Bignell, GR ;
Cox, C ;
Stephens, P ;
Edkins, S ;
Clegg, S ;
Teague, J ;
Woffendin, H ;
Garnett, MJ ;
Bottomley, W ;
Davis, N ;
Dicks, N ;
Ewing, R ;
Floyd, Y ;
Gray, K ;
Hall, S ;
Hawes, R ;
Hughes, J ;
Kosmidou, V ;
Menzies, A ;
Mould, C ;
Parker, A ;
Stevens, C ;
Watt, S ;
Hooper, S ;
Wilson, R ;
Jayatilake, H ;
Gusterson, BA ;
Cooper, C ;
Shipley, J ;
Hargrave, D ;
Pritchard-Jones, K ;
Maitland, N ;
Chenevix-Trench, G ;
Riggins, GJ ;
Bigner, DD ;
Palmieri, G ;
Cossu, A ;
Flanagan, A ;
Nicholson, A ;
Ho, JWC ;
Leung, SY ;
Yuen, ST ;
Weber, BL ;
Siegler, HF ;
Darrow, TL ;
Paterson, H ;
Marais, R ;
Marshall, CJ ;
Wooster, R .
NATURE, 2002, 417 (6892) :949-954