Resistance to MEK inhibitors: Should we co-target upstream?

Science Signaling

Volumn 4, Issue 166, 2011, Pages

  Poulikakos, Poulikos I ^a   Solit, David B ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PLX 4032; PROTEIN SERINE THREONINE KINASE INHIBITOR; RAF PROTEIN; SELUMETINIB; SOMATOMEDIN C; BRAF PROTEIN, HUMAN; KRAS PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE KINASE; ONCOPROTEIN; PROTEIN KINASE INHIBITOR; RAS PROTEIN;

CANCER CELL CULTURE; CANCER INHIBITION; CANCER RESISTANCE; CELL GROWTH; COLORECTAL CANCER; COMPETITIVE INHIBITION; DIMERIZATION; DRUG EFFICACY; DRUG SENSITIVITY; ENZYME ACTIVITY; ENZYME STABILITY; HUMAN; MELANOMA; METASTASIS; MOLECULAR DYNAMICS; NEGATIVE FEEDBACK; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; TUMOR REGRESSION; ANIMAL; DRUG ANTAGONISM; DRUG EFFECT; DRUG RESISTANCE; ENZYMOLOGY; METABOLISM; NEOPLASM;

ANIMALS; DRUG RESISTANCE, NEOPLASM; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HUMANS; MAP KINASE SIGNALING SYSTEM; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS B-RAF; RAS PROTEINS;

EID: 79953234255     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2001948     Document Type: Review

References (23)

1. K. T. Flaherty, I. Puzanov, K. B. Kim, A. Ribas, G. A. McArthur, J. A. Sosman, P. J. O'Dwyer, R. J. Lee, J. F. Grippo, K. Nolop, P. B. Chapman, Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809-819 (2010).
2. H. A. R. Kefford, M. P. Brown, M. Millward, J. R. Infante, G. V. Long, D. Ouellet, M. Curtis, P. F. Lebowitz, G. S. Falchook, Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. J. Clin. Oncol. (Meeting Abstracts), abstr. 8503 (2010).
3. J. R. Infante, L. A. Fecher, S. Nallapareddy, M. S. Gordon, K. T. Flaherty, D. S. Cox, D. J. DeMarini, S. R. Morris, H. A. Burris, W. A. Messersmith, Safety and efficacy results from the first-in-human study of the oral MEK 1/2 inhibitor GSK1120212. J. Clin. Oncol. (Meeting Abstracts), abstr. 2503 (2010).
4. P. I. Poulikakos, N. Rosen, Mutant BRAF melanomas - dependence and resistance. Cancer Cell 19, 11-15 (2011).
5. A. S. Little, K. Balmanno, M. J. Sale, S. Newman, J. R. Dry, M. Hampson, P. A.W. Edwards, P. D. Smith, S. J. Cook, Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells. Sci. Signal. 4, ra17 (2011).
6. G. Bollag, P. Hirth, J. Tsai, J. Zhang, P. N. Ibrahim, H. Cho, W. Spevak, C. Zhang, Y. Zhang, G. Habets, E. A. Burton, B. Wong, G. Tsang, B. L. West, B. Powell, R. Shellooe, A. Marimuthu, H. Nguyen, K. Y. Zhang, D. R. Artis, J. Schlessinger, F. Su, B. Higgins, R. Iyer, K. D'Andrea, A. Koehler, M. Stumm, P. S. Lin, R. J. Lee, J. Grippo, I. Puzanov, K. B. Kim, A. Ribas, G. A. McArthur, J. A. Sosman, P. B. Chapman, K. T. Flaherty, X. Xu, K. L. Nathanson, K. Nolop, Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 467, 596-599 (2010).
7. R. B. Corcoran, D. Dias-Santagata, K. Bergethon, A. J. Iafrate, J. Settleman, J. A. Engelman, BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Sci. Signal. 3, ra84 (2010).
8. Y. Wang, K. Van Becelaere, P. Jiang, S. Przybranowski, C. Omer, J. Sebolt-Leopold, A role for Kras in conferring resistance to the MEK inhibitor, CI-1040. Neoplasia 7, 336-347 (2005).
9. D. B. Solit, L. A. Garraway, C. A. Pratilas, A. Sawai, G. Getz, A. Basso, Q. Ye, J. M. Lobo, Y. She, I. Osman, T. R. Golub, J. Sebolt-Leopold, W. R. Sellers, N. Rosen, BRAF mutation predicts sensitivity to MEK inhibition. Nature 439, 358-362 (2006).
10. E. Halilovic, Q. B. She, Q. Ye, R. Pagliarini, W. R. Sellers, D. B. Solit, N. Rosen, PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and mutant KRAS signaling. Cancer Res. 70, 6804-6814 (2010).
11. R. Nazarian, H. Shi, Q. Wang, X. Kong, R. C. Koya, H. Lee, Z. Chen, M. K. Lee, N. Attar, H. Sazegar, T. Chodon, S. F. Nelson, G. McArthur, J. A. Sosman, A. Ribas, R. S. Lo, Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468, 973-977 (2010).
12. J. Villanueva, A. Vultur, J. T. Lee, R. Somasundaram, M. Fukunaga-Kalabis, A. K. Cipolla, B. Wubbenhorst, X. Xu, P. A. Gimotty, D. Kee, A. E. Santiago-Walker, R. Letrero, K. D'Andrea, A. Pushparajan, J. E. Hayden, K. D. Brown, S. Laquerre, G. A. McArthur, J. A. Sosman, K. L. Nathanson, M. Herlyn, Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell 18, 683-695 (2010).
13. C. M. Johannessen, J. S. Boehm, S. Y. Kim, S. R. Thomas, L. Wardwell, L. A. Johnson, C. M. Emery, N. Stransky, A. P. Cogdill, J. Barretina, G. Caponigro, H. Hieronymus, R. R. Murray, K. Salehi-Ashtiani, D. E. Hill, M. Vidal, J. J. Zhao, X. Yang, O. Alkan, S. Kim, J. L. Harris, C. J. Wilson, V. E. Myer, P. M. Finan, D. E. Root, T. M. Roberts, T. Golub, K. T. Flaherty, R. Dummer, B. L. Weber, W. R. Sellers, R. Schlegel, J. A. Wargo, W. C. Hahn, L. A. Garraway, COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468, 968-972 (2010).
14. E. W. Joseph, C. A. Pratilas, P. I. Poulikakos, M. Tadi, W. Wang, B. S. Taylor, E. Halilovic, Y. Persaud, F. Xing, A. Viale, J. Tsai, P. B. Chapman, G. Bollag, D. B. Solit, N. Rosen, The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner. Proc. Natl. Acad. Sci. U.S.A. 107, 14903-14908 (2010).
15. G. Hatzivassiliou, K. Song, I. Yen, B. J. Brandhuber, D. J. Anderson, R. Alvarado, M. J. Ludlam, D. Stokoe, S. L. Gloor, G. Vigers, T. Morales, I. Aliagas, B. Liu, S. Sideris, K. P. Hoeflich, B. S. Jaiswal, S. Seshagiri, H. Koeppen, M. Belvin, L. S. Friedman, S. Malek, RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 464, 431-435 (2010).
16. S. J. Heidorn, C. Milagre, S. Whittaker, A. Nourry, I. Niculescu-Duvas, N. Dhomen, J. Hussain, J. S. Reis-Filho, C. J. Springer, C. Pritchard, R. Marais, Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 140, 209-221 (2010).
17. P. I. Poulikakos, C. Zhang, G. Bollag, K. M. Shokat, N. Rosen, RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 464, 427-430 (2010).
18. O. E. Sturm, R. Orton, J. Grindlay, M. Birtwistle, V. Vyshemirsky, D. Gilbert, M. Calder, A. Pitt, B. Kholodenko, W. Kolch, The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier. Sci. Signal. 3, ra90 (2010).
19. K. H. Paraiso, I. V. Fedorenko, L. P. Cantini, A. C. Munko, M. Hall, V. K. Sondak, J. L. Messina, K. T. Flaherty, K. S. Smalley, Recovery of phospho- ERK activity allows melanoma cells to escape from BRAF inhibitor therapy. Br. J. Cancer 102, 1724-1730 (2010).
20. C. M. Emery, K. G. Vijayendran, M. C. Zipser, A. M. Sawyer, L. Niu, J. J. Kim, C. Hatton, R. Chopra, P. A. Oberholzer, M. B. Karpova, L. E. MacConaill, J. Zhang, N. S. Gray, W. R. Sellers, R. Dummer, L. A. Garraway, MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc. Natl. Acad. Sci. U.S.A. 106, 20411-20416 (2009).
21. A. B. Turke, K. Zejnullahu, Y. L. Wu, Y. Song, D. Dias-Santagata, E. Lifshits, L. Toschi, A. Rogers, T. Mok, L. Sequist, N. I. Lindeman, C. Murphy, S. Akhavanfard, B. Y. Yeap, Y. Xiao, M. Capelletti, A. J. Iafrate, C. Lee, J. G. Christensen, J. A. Engelman, P. A. Jänne, Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 17, 77-88 (2010).
22. P. M. LoRusso, S. S. Krishnamurthi, J. J. Rinehart, L. M. Nabell, L. Malburg, P. B. Chapman, S. E. DePrimo, S. Bentivegna, K. D. Wilner, W. Tan, A. D. Ricart, Phase I pharmacokinetic and pharmacodynamic study of the oral MAPK/ERK kinase inhibitor PD-0325901 in patients with advanced cancers. Clin. Cancer Res. 16, 1924-1937 (2010).
23. Competing interests: D.B.S. has served as a consultant for AstraZeneca and Roche.