RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

Nature

Volumn 464, Issue 7287, 2010, Pages 431-435

  Hatzivassiliou, Georgia ^a   Song, Kyung ^a   Yen, Ivana ^a   Brandhuber, Barbara J ^b   Anderson, Daniel J ^a   Alvarado, Ryan ^a   Ludlam, Mary J C ^a   Stokoe, David ^a   Gloor, Susan L ^b   Vigers, Guy ^b   Morales, Tony ^b   Aliagas, Ignacio ^a   Liu, Bonnie ^a   Sideris, Steve ^a   Hoeflich, Klaus P ^a   Jaiswal, Bijay S ^a   Seshagiri, Somasekar ^a   Koeppen, Hartmut ^a   Belvin, Marcia ^a   Friedman, Lori S ^a   Malek, Shiva ^a   more..

^a GENENTECH INC   (United States)

^b ARRAY BIOPHARMA INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; GUANOSINE TRIPHOSPHATE; MITOGEN ACTIVATED PROTEIN KINASE; RAF INHIBITOR; RAF PROTEIN; RAS ASSOCIATION DOMAIN FAMILY PROTEIN 1A; UNCLASSIFIED DRUG;

CANCER; DISEASE TREATMENT; GENE EXPRESSION; GENETIC ANALYSIS; INHIBITOR; MUTATION; PROTEIN; TUMOR;

ARTICLE; CANCER GRAFT; CANCER MODEL; DIMERIZATION; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME INHIBITION; MUTANT; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TUMOR GROWTH; WILD TYPE; XENOGRAFT;

ADENOSINE TRIPHOSPHATE; ANIMALS; BENZAMIDES; CELL LINE; CELL MEMBRANE; CELL PROLIFERATION; DIPHENYLAMINE; ENZYME ACTIVATION; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HUMANS; INDENES; INDOLES; MAP KINASE SIGNALING SYSTEM; MICE; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS B-RAF; PROTO-ONCOGENE PROTEINS C-RAF; PYRAZOLES; RAF KINASES; RAS PROTEINS; SULFONAMIDES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77949685981     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature08833     Document Type: Article

References (33)

1. Schubbert, S., Shannon, K. & Bollag, G. Hyperactive Ras in developmental disorders and cancer. Nature Rev. Cancer 7, 295-308 (2007).
2. Yeh, J. J. et al. KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer. Mol. Cancer Ther. 8, 834-843 (2009).
3. Hoeflich, K. P. et al. 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. Cancer Res. 69, 3042-3051 (2009).
4. Hansen, J. D. et al. Potent and selective pyrazole-based inhibitors of B-Raf kinase. Bioorg. Med. Chem. Lett. 18, 4692-4695 (2008).
5. Tsai, J. et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl Acad. Sci. USA 105, 3041-3046 (2008).
6. Malek, S. Selective inhibition of Raf results in downregulation of the RAS/RAF/ MEK/ERK pathway and inhibition of tumor growth in vivo. Eur. J. Cancer, Suppl. 4, 184 (2006).
7. Flaherty, K. et al. Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J. Clin. Oncol. 27, abstract 9000 (2009).
8. Schwartz, G. K. etal. A phase I study of XL281, a selective oral RAF kinase inhibitor, in patients (Pts) with advanced solid tumors. J. Clin. Oncol. 27, abstract 3513 (2009).
9. Chapman, P. et al. Early efficacy signal demonstrated in advanced melanoma in a phase I trial of the oncogenic BRAF-selective inhibitor PLX4032. Eur. J. Cancer, Suppl. 7, 5 (2009).
10. Jaiswal, B. S. et al. Combined targeting of BRAF and CRAF or BRAF and PI3K effector pathways is required for efficacy in NRAS mutant tumors. PLoS One 4, e5717 (2009).
11. Garnett, M. J. et al. Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization. Mol. Cell 20, 963-969 (2005).
12. Rushworth, L. K., Hindley, A. D., O'Neill, E. & Kolch, W. Regulation and role of Raf-1/B-Raf heterodimerization. Mol. Cell. Biol. 26, 2262-2272 (2006).
13. Weber, C. K., Slupsky, J. R., Kalmes, H. A. & Rapp, U. R. Active Ras induces heterodimerization of cRaf and BRaf. Cancer Res. 61, 3595-3598 (2001).
14. Wan, P. T. et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116, 855-867 (2004).
15. Kim, J. S., Lee, C., Foxworth, A. & Waldman, T. B-Raf is dispensable for K-Ras-mediated oncogenesis in human cancer cells. Cancer Res. 64, 1932-1937 (2004).
16. Yun, J. et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325, 1555-1559 (2009).
17. Zang, M. et al. Characterization of Ser338 phosphorylation for Raf-1 activation. J. Biol. Chem. 283, 31429-31437 (2008).
18. Khazak, V., Astsaturov, I., Serebriiskii, I. G. & Golemis, E. A. Selective Raf inhibition in cancer therapy. Expert Opin. Ther. Targets 11, 1587-1609 (2007).
19. Goetz, C. A., O'Neil, J. J. & Farrar, M. A. Membrane localization, oligomerization, and phosphorylation are required for optimal raf activation. J. Biol. Chem. 278, 51184-51189 (2003).
20. Xiang, X. et al. Phosphorylation of 338SSYY341 regulates specific interaction between Raf-1 and MEK1. J. Biol. Chem. 277, 44996-45003 (2002).
21. Terai, K. & Matsuda, M. Ras binding opens c-Raf to expose the docking site for mitogen-activated protein kinase kinase. EMBO Rep. 6, 251-255 (2005).
22. Jelinek, T. et al. RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2. Mol. Cell. Biol. 14, 8212-8218 (1994).
23. Cameron, A. J. et al. PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity. Nature Struct. Mol. Biol. 16, 624-630 (2009).
24. Okuzumi, T. et al. Inhibitor hijacking of Akt activation. Nature Chem. Biol. 5, 484-493 (2009).
25. Hindie, V. et al. Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1. Nature Chem. Biol. 5, 758-764 (2009).
26. Rajakulendran, T. et al. A dimerization-dependent mechanism drives RAF catalytic activation. Nature 461, 542-545 (2009).
27. Wellbrock, C., Karasarides, M. & Marais, R. The RAF proteins take centre stage. Nature Rev. Mol. Cell Biol. 5, 875-885 (2004).
28. Wallace, E. M. et al. Potent and selective mitogen-activated protein kinase kinase (MEK) 1,2 inhibitors. 1. 4-(4-bromo-2-fluorophenylamino)-1- methylpyridin-2(1H)-ones. J. Med. Chem. 49, 441-444 (2006).
29. Cheng, Y. & Prusoff, W. H. Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099-3108 (1973).
30. Lukyanov, K. A. et al. Natural animal coloration can be determined by a nonfluorescent green fluorescent protein homolog. J. Biol. Chem. 275, 25879-25882 (2000).
31. Matz, M. V. et al. Fluorescent proteins from nonbioluminescent Anthozoa species. Nature Biotechnol. 17, 969-973 (1999).
32. Stokoe, D. & McCormick, F. Activation of c-Raf-1 by Ras and Src through different mechanisms: activation in vivo and in vitro. EMBO J. 16, 2384-2396 (1997).
33. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50, 760-763 (1994).