Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2

被引：6

作者：

Chen, Wenjing ^{[1
]}

Park, Jong-In ^{[1
]}

机构：

[1] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 19期

关键词：

BRAF; MEK; tumor; drug resistance; MUTANT COLORECTAL-CANCER; ACQUIRED-RESISTANCE; MAPK PATHWAY; CONFERS RESISTANCE; IMMUNE MICROENVIRONMENT; METASTATIC MELANOMA; FEEDBACK ACTIVATION; RAF INHIBITION; KINASE; DABRAFENIB;

D O I：

10.3390/ijms241914837

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

BRAF is one of the most frequently mutated oncogenes, with an overall frequency of about 50%. Targeting BRAF and its effector mitogen-activated protein kinase kinase 1/2 (MEK1/2) is now a key therapeutic strategy for BRAF-mutant tumors, and therapies based on dual BRAF/MEK inhibition showed significant efficacy in a broad spectrum of BRAF tumors. Nonetheless, BRAF/MEK inhibition therapy is not always effective for BRAF tumor suppression, and significant challenges remain to improve its clinical outcomes. First, certain BRAF tumors have an intrinsic ability to rapidly adapt to the presence of BRAF and MEK1/2 inhibitors by bypassing drug effects via rewired signaling, metabolic, and regulatory networks. Second, almost all tumors initially responsive to BRAF and MEK1/2 inhibitors eventually acquire therapy resistance via an additional genetic or epigenetic alteration(s). Overcoming these challenges requires identifying the molecular mechanism underlying tumor cell resistance to BRAF and MEK inhibitors and analyzing their specificity in different BRAF tumors. This review aims to update this information.

引用

页数：17

共 126 条

[41] Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma [J].

Girotti, Maria R. ;

Pedersen, Malin ;

Sanchez-Laorden, Berta ;

Viros, Amaya ;

Turajlic, Samra ;

Niculescu-Duvaz, Dan ;

Zambon, Alfonso ;

Sinclair, John ;

Hayes, Andrew ;

Gore, Martin ;

Lorigan, Paul ;

Springer, Caroline ;

Larkin, James ;

Jorgensen, Claus ;

Marais, Richard .

CANCER DISCOVERY, 2013, 3 (02) :158-167

[42] Patient and Tumor Characteristics and BRAF and KRAS Mutations in Colon Cancer, NCCTG/Alliance N0147 [J].

Gonsalves, Wilson I. ;

Mahoney, Michelle R. ;

Sargent, Daniel J. ;

Nelson, Garth D. ;

Alberts, Steven R. ;

Sinicrope, Frank A. ;

Goldberg, Richard M. ;

Limburg, Paul J. ;

Thibodeau, Stephen N. ;

Grothey, Axel ;

Hubbard, Joleen M. ;

Chan, Emily ;

Nair, Suresh ;

Berenberg, Jeffrey L. ;

McWilliams, Robert R. .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2014, 106 (07)

[43] Combinations of BRAF, MEK, and PI3K/mTOR Inhibitors Overcome Acquired Resistance to the BRAF Inhibitor GSK2118436 Dabrafenib, Mediated by NRAS or MEK Mutations [J].

Greger, James G. ;

Eastman, Stephen D. ;

Zhang, Vivian ;

Bleam, Maureen R. ;

Hughes, Ashley M. ;

Smitheman, Kimberly N. ;

Dickerson, Scott H. ;

Laquerre, Sylvie G. ;

Liu, Li ;

Gilmer, Tona M. .

MOLECULAR CANCER THERAPEUTICS, 2012, 11 (04) :909-920

[44] Molecular Pathways: BRAF Induces Bioenergetic Adaptation by Attenuating Oxidative Phosphorylation [J].

Haq, Rizwan ;

Fisher, David E. ;

Widlund, Hans R. .

CLINICAL CANCER RESEARCH, 2014, 20 (09) :2257-2263

[45] Oncogenic BRAF Regulates Oxidative Metabolism via PGC1α and MITF [J].

Haq, Rizwan ;

Shoag, Jonathan ;

Andreu-Perez, Pedro ;

Yokoyama, Satoru ;

Edelman, Hannah ;

Rowe, Glenn C. ;

Frederick, Dennie T. ;

Hurley, Aeron D. ;

Nellore, Abhinav ;

Kung, Andrew L. ;

Wargo, Jennifer A. ;

Song, Jun S. ;

Fisher, David E. ;

Arany, Zolt ;

Widlund, Hans R. .

CANCER CELL, 2013, 23 (03) :302-315

[46] ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors [J].

Hatzivassiliou, Georgia ;

Liu, Bonnie ;

O'Brien, Carol ;

Spoerke, Jill M. ;

Hoeflich, Klaus P. ;

Haverty, Peter M. ;

Soriano, Robert ;

Forrest, William F. ;

Heldens, Sherry ;

Chen, Huifen ;

Toy, Karen ;

Ha, Connie ;

Zhou, Wei ;

Song, Kyung ;

Friedman, Lori S. ;

Amler, Lukas C. ;

Hampton, Garret M. ;

Moffat, John ;

Belvin, Marcia ;

Lackner, Mark R. .

MOLECULAR CANCER THERAPEUTICS, 2012, 11 (05) :1143-1154

[47] RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth [J].

Hatzivassiliou, Georgia ;

Song, Kyung ;

Yen, Ivana ;

Brandhuber, Barbara J. ;

Anderson, Daniel J. ;

Alvarado, Ryan ;

Ludlam, Mary J. C. ;

Stokoe, David ;

Gloor, Susan L. ;

Vigers, Guy ;

Morales, Tony ;

Aliagas, Ignacio ;

Liu, Bonnie ;

Sideris, Steve ;

Hoeflich, Klaus P. ;

Jaiswal, Bijay S. ;

Seshagiri, Somasekar ;

Koeppen, Hartmut ;

Belvin, Marcia ;

Friedman, Lori S. ;

Malek, Shiva .

NATURE, 2010, 464 (7287) :431-U132

[48] Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial [J].

Hauschild, Axel ;

Grob, Jean-Jacques ;

Demidov, Lev V. ;

Jouary, Thomas ;

Gutzmer, Ralf ;

Millward, Michael ;

Rutkowski, Piotr ;

Blank, Christian U. ;

Miller, Wilson H., Jr. ;

Kaempgen, Eckhart ;

Martin-Algarra, Salvador ;

Karaszewska, Boguslawa ;

Mauch, Cornelia ;

Chiarion-Sileni, Vanna ;

Martin, Anne-Marie ;

Swann, Suzanne ;

Haney, Patricia ;

Mirakhur, Beloo ;

Guckert, Mary E. ;

Goodman, Vicki ;

Chapman, Paul B. .

LANCET, 2012, 380 (9839) :358-365

[49] Convergent Therapeutic Strategies to Overcome the Heterogeneity of Acquired Resistance in &ITBRAF&ITV600E Colorectal Cancer [J].

Hazar-Rethinam, Mehlika ;

Kleyman, Marianna ;

Han, G. Celine ;

Liu, David ;

Ahronian, Leanne G. ;

Shahzade, Heather A. ;

Chen, Lifeng ;

Parikh, Aparna R. ;

Allen, Jill N. ;

Clark, Jeffrey W. ;

Kwak, Eunice L. ;

Faris, Jason E. ;

Murphy, Janet E. ;

Hong, Theodore S. ;

Van Seventer, Emily E. ;

Nadres, Brandon ;

Hong, Catriona B. ;

Gurski, Joseph M., Jr. ;

Jessop, Nicholas A. ;

Dias-Santagata, Dora ;

Iafrate, A. John ;

Van Allen, Eliezer M. ;

Corcoran, Ryan B. .

CANCER DISCOVERY, 2018, 8 (04) :417-427

[50] Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF [J].

Heidorn, Sonja J. ;

Milagre, Carla ;

Whittaker, Steven ;

Nourry, Arnaud ;

Niculescu-Duvas, Ion ;

Dhomen, Nathalie ;

Hussain, Jahan ;

Reis-Filho, Jorge S. ;

Springer, Caroline J. ;

Pritchard, Catrin ;

Marais, Richard .

CELL, 2010, 140 (02) :209-221

← 1 2 3 4 5 6 7 8 9 10 →