Vemurafenib (RG67204, PLX4032): A potent, selective BRAF kinase inhibitor

Future Oncology

Volumn 8, Issue 5, 2012, Pages 509-523

  Patrawala, Samit ^a   Puzanov, Igor ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

BRAF; melanoma; metastatic; PLX4032; RG7204; vemurafenib; zelboraf

Indexed keywords

B RAF KINASE; B RAF KINASE INHIBITOR; DACARBAZINE; FOTEMUSTINE; INTERLEUKIN 2; IPILIMUMAB; MITOGEN ACTIVATED PROTEIN KINASE; RG67204; TEMOZOLOMIDE; UNCLASSIFIED DRUG; VEMURAFENIB;

ACTINIC KERATOSIS; ALOPECIA; ANOREXIA; AREA UNDER THE CURVE; ARTHRALGIA; ASTHENIA; BACKACHE; BRAIN METASTASIS; CANCER GROWTH; CANCER IMMUNOTHERAPY; CANCER INHIBITION; CANCER INVASION; CANCER MORTALITY; CANCER SURVIVAL; CONSTIPATION; COUGHING; DIARRHEA; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG STRUCTURE; DRUG WITHDRAWAL; DRY SKIN; DYSESTHESIA; DYSGEUSIA; ERYTHEMA; FATIGUE; FEVER; GENE EXPRESSION; GENE MUTATION; HEADACHE; HUMAN; HYPERKERATOSIS; KERATOACANTHOMA; LIMB PAIN; MACULOPAPULAR RASH; METASTATIC MELANOMA; MULTIPLE CYCLE TREATMENT; MUSCULOSKELETAL PAIN; MYALGIA; NAUSEA; NEUTROPENIA; NONHUMAN; OVERALL SURVIVAL; PAPULAR RASH; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHOTOSENSITIVITY; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN PHOSPHORYLATION; PRURITUS; RASH; REVIEW; RISK REDUCTION; SEBORRHEIC KERATOSIS; SIDE EFFECT; SKIN CARCINOMA; SKIN PAPILLOMA; SUNBURN; TREATMENT RESPONSE; VOMITING;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; HUMANS; INDOLES; MELANOMA; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; SULFONAMIDES;

EID: 84861743320     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.12.31     Document Type: Review

References (30)

1. Puzanov I, Flaherty KT, Sosman JA et al. Vemurafenib. Drugs Future 36(3), 191-199 (2011).
2. Sebolt-Leopold JS, Herrera R. Targeting the mitogen-Activated protein kinase cascade to treat cancer. Nat. Rev. Cancer 4(12), 937-947 (2004). (Pubitemid 39626217)
3. McCubrey JA, Steelman LS, Chappell WH et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim. Biophys. Acta 1773(8), 1263-1284 (2007). (Pubitemid 47125967)
4. Wan PT, Garnett MJ, Roe SM et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116(6), 855-867 (2004). (Pubitemid 38410730)
5. Hoeflich KP, Herter S, Tien J 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(7), 3042-3051 (2009).
6. Zhang BH, Guan KL. Activation of B-Raf kinase requires phosphorylation of the conserved residues Thr598 and Ser601. EMBO J. 19(20), 5429-5439 (2000).
7. Goydos JS, Mann B, Kim HJ et al. Detection of B-RAF and N-RAS mutations in human melanoma. J. Am. Coll. Surg. 200(3), 362-370 (2005). (Pubitemid 40298970)
8. Libra M, Malaponte G, Navolanic PM et al. Analysis of BRAF mutation in primary and metastatic melanoma. Cell Cycle 4(10), 1382-1384 (2005). (Pubitemid 41437127)
9. Garnett MJ, Marais R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6(4), 313-319 (2004). (Pubitemid 39361432)
10. Fransen K, Klintenas M, Osterstrom A, Dimberg J, Monstein HJ, Soderkvist P. Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis 25(4), 527-533 (2004). (Pubitemid 38528645)
11. Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature 417(6892), 949-954 (2002). (Pubitemid 34716871)
12. Ewalt M, Nandula S, Phillips A et al. Real-Time PCR-based analysis of BRAF V600E mutation in low and intermediate grade lymphomas confirms frequent occurrence in hairy cell leukaemia. Hematol. Oncol. doi:10.1002/hon.1023 (2011) (Epub ahead of print).
13. Badalian-Very G, Vergilio JA, Degar BA et al. Recurrent BRAF mutations in langerhans cell histiocytosis. Blood 116(11), 1919-1923 (2010).
14. Bollag G, Hirth P, Tsai J et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 467(7315), 596-599 (2010).
15. Yang H, Higgins B, Kolinsky K et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models. Cancer Res. 70(13), 5518-5527 (2010).
16. Flaherty KT, Puzanov I, Kim KB et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363(9), 809-819 (2010).
17. Kopetz S, Desai J, Chan E et al. PLX4032 in metastatic colorectal cancer patients with mutant BRAF tumors. J. Clin. Oncol. 28(Suppl. 15), Abstract 3534 (2010).
18. McArthur GA, Puzanov I, Ribas A et al. Early FDG-PET responses to PLX4032 in BRAF-mutant advanced melanoma. J. Clin. Oncol. 28(Suppl. 15), Abstract 8529 (2010).
19. Sosman J, Kim K, Schuchter L et al. An open-label, multicenter Phase II study of continuous oral dosing of RG7204 (PLX4032) in previously treated patients with BRAF V600E mutation-positive metastatic melanoma. N. Engl. J. Med. 366(8), 707-714 (2012).
20. Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364(26), 2507-2516 (2011).
21. Dummer J, Rinderknecht J, Goldinger SM et al. An open-label pilot study of vemurafenib in previously treated metastatic melanoma patients with brain metastases. J. Clin. Oncol. 29(Suppl.), Abstract 8548 (2011).
22. Hatzivassiliou G, Song K, Yen I et al. RAF inhibitors prime wild-Type RAF to activate the MAPK pathway and enhance growth. Nature 464(7287), 431-435 (2010).
23. Heidorn SJ, Milagre C, Whittaker S et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 140(2), 209-221 (2010).
24. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-Type BRAF. Nature 464(7287), 427-430 (2010).
25. Nazarian R, Shi H, Wang Q et al. Melanomas acquire resistance to B-RAF (V600E) inhibition by RTK or N-RAS upregulation. Nature 468(7326), 973-977 (2010).
26. Villanueva J, Vultur A, Lee JT et al. 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(6), 683-695 (2010).
27. Smalley KS, Haass NK, Brafford PA, Lioni M, Flaherty KT, Herlyn M. Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Mol. Cancer Ther. 5(5), 1136-1144 (2006). (Pubitemid 43881305)
28. Lasithiotakis KG, Sinnberg TW, Schittek B et al. Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells. J. Invest. Dermatol. 128(8), 2013-2023 (2008). (Pubitemid 352001225)
29. Johannessen CM, Boehm JS, Kim SY et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468(7326), 968-972 (2010).
30. Su F, Viros A, Milagre C et al. Ras mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N. Engl. J. Med. 366(3), 207-215 (2012).