BRAF in metastatic colorectal cancer: The future starts now

Pharmacogenomics

Volumn 16, Issue 18, 2015, Pages 2069-2081

  Orlandi, Armando ^a,b,c   Calegari, Maria Alessandra ^a   Inno, Alessandro ^b   Berenato, Rosa ^c   Caporale, Marta ^c   Niger, Monica ^c   Bossi, Ilaria ^c   Bartolomeo, Maria Di ^c   Braud, Filippo De ^c   Pietrantonio, Filippo ^c  

^a CATHOLIC UNIVERSITY   (Italy)

^b SACRO CUORE DON CALABRIA HOSPITAL   (Italy)

^c NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

BRAF; colorectal cancer; immunotherapy; target therapy

Indexed keywords

ALPELISIB; ANTINEOPLASTIC AGENT; B RAF KINASE; B RAF KINASE INHIBITOR; BEVACIZUMAB; CEP 32496; CETUXIMAB; DABRAFENIB; ENCORAFENIB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; MITOGEN ACTIVATED PROTEIN KINASE KINASE INHIBITOR; OXALIPLATIN; PANITUMUMAB; PROTEIN TYROSINE KINASE INHIBITOR; REGORAFENIB; TRAMETINIB; UNCLASSIFIED DRUG; VEMURAFENIB; WNT 974; XL 281; BRAF PROTEIN, HUMAN;

ADD ON THERAPY; CANCER CHEMOTHERAPY; CANCER PATIENT; CANCER PROGNOSIS; DATA ANALYSIS; DIARRHEA; DRUG EFFICACY; DRUG ERUPTION; DRUG RESPONSE; DRUG TARGETING; FATIGUE; GENE MUTATION; HUMAN; LOADING DRUG DOSE; MELANOMA; METASTATIC COLORECTAL CANCER; METASTATIC MELANOMA; NAUSEA; RETROSPECTIVE STUDY; REVIEW; CLINICAL TRIAL (TOPIC); COLORECTAL NEOPLASMS; GENETICS; IMMUNOLOGY; METABOLISM; METASTASIS; MOLECULARLY TARGETED THERAPY; PROGNOSIS;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; COLORECTAL NEOPLASMS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM METASTASIS; PROGNOSIS; PROTO-ONCOGENE PROTEINS B-RAF;

EID: 84948954584     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/pgs.15.140     Document Type: Review

References (65)

1. Mercer KE, Pritchard CA. Raf proteins and cancer: B-Raf is identified as a mutational target. Biochim. Biophys. Acta 1653, 25-40 (2003).
2. Sclafani F, Gullo G, Sheahan K, Crown J. BRAF mutations in melanoma and colorectal cancer: a single oncogenic mutation with different tumour phenotypes and clinical implications. Crit. Rev. Oncol. Hematol. 87, 55-68 (2013).
3. Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 410, 37-40 (2001).
4. Peyssonnaux C, Eychene A. The Raf/MEK/ERK pathway: new concepts of activation. Biol. Cell. 93, 53-62 (2001).
5. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 103(2), 211-225 (2000).
6. Chong H, Vikis HG, Guan KL. Mechanisms of regulating the Raf kinase family. Cell Signal. 15, 463-469 (2003).
7. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 144, 646-674 (2011).
8. Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature 417, 949-954 (2002).
9. 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, 527-533 (2004).
10. Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N. Engl. J. Med. 361(1), 98-99 (2009).
11. Zhang BH, Guan KL. Activation of B-Raf kinase requires phosphorylation of the conserved residues Thr598 and Ser601. EMBO J. 19, 5429-5439 (2000).
12. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature (Lond.) 418, 934 (2002).
13. Yuen ST, Davies H, Chan TL et al. Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res. 62, 6451-6455 (2002).
14. Hall RD, Kudchadkar RR. BRAF mutations: signaling, epidemiology, and clinical experience in multiple malignancies. Cancer Control 221, 221-231 (2014).
15. Samowitz WS, Sweeney C, Herrick J et al. Poor survival associated with the BRAF V600E mutation in microsatellitestable colon cancers. Cancer Res. 65, 6063-6069 (2005).
16. Tran B, Kopetz S, Tie J, Gibbs P et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 117(20), 4623-4632 (2011).
17. Saridaki Z, Tzardi M, Sfakianaki M et al. BRAFV600E mutation analysis in patients with metastatic colorectal cancer (mCRC) in daily clinical practice: correlations with clinical characteristics, and its impact on patients' outcome. PLoS ONE 8(12), e84604 (2013).
18. Richman SD, Seymour MT, Chambers P et al. KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J. Clin. Oncol. 127(35), 5931-5937 (2009).
19. Douillard JY, Oliner KS, Siena S et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N. Engl. J. Med. 369(11), 1023-1034 (2013).
20. Van Cutsem E, Lenz HJ, Köhne CH et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J. Clin. Oncol. 33(7), 692-700 (2015).
21. Mao C, Liao R-Y, Qiu L-X et al. BRAF V600E mutation and resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer: a meta-analysis. Mol. Biol. Rep. 38, 2219-2223 (2011).
22. Bokemeyer C, Van Cutsem E, Rougier P et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur. J. Cancer 48, 1466-1475 (2012).
23. Yuan Z-X, Wang X-Y, Qin Q-Y et al. The prognostic role of BRAF mutation in metastatic colorectal cancer receiving anti-EGFR monoclonal antibodies: a meta-analysis. PLoS ONE 8, e65995 (2013).
24. Cui D, Cao D, Yang Y et al. Effect of BRAF V600E mutation on tumor response of anti-EGFR monoclonal antibodies for first-line metastatic colorectal cancertreatment: a meta-analysis of randomized studies. Mol. Biol. Rep. 41, 1291-1298 (2014).
25. Therkildsen C, Bergmann T, Henrichsen-Schnack T et al. The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: a systematic review and meta-analysis. Acta Oncol. 53, 852-864 (2014).
26. Wang Q, Hu WG, Song QB, Wei J. BRAF V600E mutation as a predictive factor of anti-EGFR monoclonal antibodies therapeutic effects in metastatic colorectal cancer: a metaanalysis. Chin. Med. Sci. J. 29, 197-203 (2014).
27. Pietrantonio F, Petrelli F, Coinu A et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur. J. Cancer 51(5), 587-594 (2015).
28. Masi G, Loupakis F, Salvatore L et al. Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a Phase 2 trial. Lancet Oncol. 11(9), 845-852 (2010).
29. Loupakis F, Cremolini C, Salvatore L et al. FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer. Eur. J. Cancer 50, 57-63 (2014).
30. Loupakis F, Cremolini C, Masi G et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N. Engl. J. Med. 371(17), 1609-1618 (2014).
31. Loupakis F, Cremolini C, Lonardi S et al. Subgroup analyses in RAS mutant, BRAF mutant and all-wt mCRC pts treated with FOLFOXIRI plus bevacizumab (bev) or FOLFOXIRI plus bev in the TRIBE study. J. Clin. Oncol. 32(Suppl. 5s), Abstract 3519 (2014).
32. Basso M, Strippoli A, Orlandi A et al. KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC1 expression in metastatic colorectal cancer patients. Br. J. Cancer 108(1), 115-120 (2013).
33. Orlandi A, Di Salvatore M, Bagalà C et al. ERCC1 induction after oxaliplatin exposure may depend on KRAS mutational status in colorectal cancer cell line: in vitro veritas. J. Cancer 6(1), 70-81 (2015).
34. Flaherty KT, Puzanov I, Kim KB et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809-819 (2010).
35. Long GV, Stroyakovskiy D, Gogas N et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N. Engl. J. Med. 371, 1877-1888 (2014).
36. Kopetz S, Desai J, Chan E et al. PLX4032 in metastatic colon cancer patients with mutant BRAF tumors. J. Clin. Oncol. 28(Suppl. 15s), Abstract 3534 (2010).
37. Corcoran RB, Ebi H, Turke AB et al. EGFR-mediated reactivation of MAPK signaling contribuites to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov. 2, 227-235 (2012).
38. Montero-Conde C, Ruiz-Llorente S, Dominguez JM et al. Relief of feedback inhibition of HER3 transcription by RAF and MEK inhibitors attenuates their antitumor effects in BRAF-mutant thyroid carcinomas. Cancer Discov. 3, 520-533 (2013).
39. Prahallad A, Sun C, Huang S et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483, 100-103 (2012).
40. 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, 427-430 (2010).
41. Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 464, 431-435 (2010).
42. Ahronian LG, Sennott EM, Van Allen EM et al. Clinical acquired resistance to RAF inhibitor combinations in BRAF-mutant colorectal cancer through MAPK pathway alterations. Cancer Discov. 5, 358-367 (2015).
43. Falchook GS, Long GV, Kurzrock R et al. RAF inhibitor Dabrafenib (GSK2118436) is active in melanoma brain metastases, multiple BRAF genotypes and diverse cancers. Lancet 379, 1893-1901 (2012).
44. Gomez-Roca CA, Delord J, Robert C et al. Encorafenib (LGX818), an oral BRAF inhibitor, in patients (pts) with BRAF V600E metastatic colorectal cancer (mCRC): results of dose expansion in an open-label, Phase 1 study. Ann. Oncol. 25(Suppl. 4), iv182-iv183 (2014).
45. Tabernero J, Chan E, Baselga J et al. VE-BASKET, a Simon 2-stage adaptive design, Phase II, histology-independent study in nonmelanoma solid tumors harboring BRAF V600 mutations (V600m): activity of vemurafenib (VEM) with or without cetuximab (CTX) in colorectal cancer (CRC). J. Clin. Oncol. 32(Suppl.), Abstract 3518 (2014).
46. Yaeger R, Cercek A, O'Reilly EM, Vakiani E, Saltz LB et al. Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients. Clin. Cancer Res. 21(6), 1313-1320 (2015).
47. Lacouture ME, Duvic M, Hauschild A et al. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist 18(3), 314-322 (2013).
48. Van Cutsem E, Peeters M, Siena S et al. Open-label Phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J. Clin. Oncol. 25(13), 1658-1664 (2007).
49. Lavoie H, Thevakumaran N, Gavory G et al. Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization. Nat. Chem. Biol. 9(7), 428-436 (2013).
50. Van Geel R, Elez E, Bendell JC et al. Phase I study of the selective BRAFV600 inhibitor encorafenib (LGX818) combined with cetuximab and with or without the-specific PI3K inhibitor BYL719 in patients with advanced BRAFmutant colorectal cancer. J. Clin. Oncol. 32, 5s (Suppl.; Abstract 3514) (2014).
51. Bendell JC, Atreya CE, André T et al. Efficacy and tolerability in an open-label Phase I/II study of MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in combination in patients (pts) with BRAF V600E mutated colorectal cancer (CRC). J. Clin. Oncol. 32(Suppl. 5s), Abstract 3515 (2014).
52. Hong DS, Morris VK, El Osta BE et al. Phase 1b study of vemurafenib in combination with irinotecan and cetuximab in patients with BRAF-mutated advanced cancers and advanced cancers. J. Clin. Oncol. 33(Suppl. 15), 3511 (2015).
53. Capper D, Preusser M, Habel A et al. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol. 122, 11-19 (2011).
54. Toon CW, Walsh MD, Chou A et al. BRAF V600E immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome. Am. J. Surg. Pathol. 37, 1592-1602 (2013).
55. Thiel A, Heinonen M, Kantonen J et al. BRAF mutation in sporadic colorectal cancer and Lynch syndrome. Virchows Arch. 463(5), 613-621 (2013).
56. Roskoski R Jr. RAF protein-serine/threonine kinases: structure and regulation. Biochem. Biophys. Res. Commun. 399, 313-317 (2010).
57. Saridaki Z, Papadatos-Pastos D, Tzardi M et al. BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients' outcome. Br. J. Cancer 102, 1762-1768 (2010).
58. Roth AD, Tejpar S, Delorenzi M et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J. Clin. Oncol. 28, 466-474 (2010).
59. Ogino S, Shima K, Meyerhardt JA et al. Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803. Clin. Cancer Res. 18, 890-900 (2012).
60. Pai RK, Jayachandran P, Koong AC et al. BRAF mutated, microsatellite-stable adenocarcinoma of the proximal colon: an aggressive adenocarcinoma with poor survival, mucinous differentiation, and adverse morphologic features. Am. J. Surg. Pathol. 36, 744-752 (2012).
61. Wang L, Cunningham JM, Winters JL et al. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 63, 5209-5212 (2003).
62. Kalady MF, Dejulius KL, Sanchez JA et al. BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis. Dis. Colon Rectum 55, 128-133 (2012).
63. Le DT, Uram JN, Wang H et al. PD-1 blockade in tumors with mismatch-repair deficiency N. Engl. J. Med. 372(26), 2509-2520 (2015).
64. Cremolini C, Di Bartolomeo M, Amatu A et al. BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann. Oncol. 26, 2092-2097 (2015).
65. Cremolini C, Di Maio M, Petrelli F et al. BRAF-mutated metastatic colorect cancer between past and future. Br. J. Cancer doi:10.1038/bjc.2015.316 (2015) (Epub ahead of print).