Targeting BRAF mutant metastatic colorectal cancer: clinical implications and emerging therapeutic strategies

Targeted Oncology

Volumn 10, Issue 2, 2015, Pages 179-188

  Tie, Jeanne ^a,b,c   Desai, Jayesh ^a,b,c,d  

^a LUDWIG INSTITUTE FOR CANCER RESEARCH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c ROYAL MELBOURNE HOSPITAL   (Australia)

^d PETER MACCALLUM CANCER CENTRE   (Australia)

Author keywords

Biomarker; BRAF; Colorectal cancer; Resistance mechanism; Targeted therapy

Indexed keywords

8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; ANTINEOPLASTIC AGENT; B RAF KINASE; B RAF KINASE INHIBITOR; BEVACIZUMAB; CAPECITABINE; CETUXIMAB; DACARBAZINE; ERLOTINIB; GEFITINIB; IRINOTECAN; K RAS PROTEIN; N [3 (5 CHLORO 1H PYRROLO[2,3 B]PYRIDINE 3 CARBONYL) 2,4 DIFLUOROPHENYL]PROPANESULFONAMIDE; OXALIPLATIN; VEMURAFENIB; BRAF PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR;

ANTINEOPLASTIC ACTIVITY; BRAF GENE; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER PROGNOSIS; CANCER STAGING; CARCINOGENESIS; CPG ISLAND; DISEASE FREE SURVIVAL; DRUG EFFICACY; DRUG SAFETY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; FATIGUE; GENE EXPRESSION; GENE MUTATION; GENE TARGETING; HUMAN; KRAS GENE; MELANOMA; METASTASIS; METASTATIC COLORECTAL CANCER; MICROSATELLITE INSTABILITY; MOLECULARLY TARGETED THERAPY; NONHUMAN; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHENOTYPE; PHOTOSENSITIVITY; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROMOTER REGION; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RECURRENCE FREE SURVIVAL; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; COLORECTAL NEOPLASMS; DNA MUTATIONAL ANALYSIS; DRUG EFFECTS; DRUG RESISTANCE; ENZYMOLOGY; GENETIC PREDISPOSITION; GENETICS; METABOLISM; MUTATION; PATHOLOGY; PERSONALIZED MEDICINE; PREDICTIVE VALUE;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; COLORECTAL NEOPLASMS; DNA MUTATIONAL ANALYSIS; DRUG RESISTANCE, NEOPLASM; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASM METASTASIS; PHENOTYPE; PRECISION MEDICINE; PREDICTIVE VALUE OF TESTS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; SIGNAL TRANSDUCTION;

EID: 84930539609     PISSN: 17762596     EISSN: 1776260X     Source Type: Journal    
DOI: 10.1007/s11523-014-0330-0     Document Type: Review

References (78)

1. Samowitz WS, Sweeney C, Herrick J, Albertsen H, Levin TR, Murtaugh MA et al (2005) Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res 65(14):6063–6069
2. Tie J, Gibbs P, Lipton L, Christie M, Jorissen RN, Burgess AW et al (2011) Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation. Int J Cancer 128(9):2075–2084
3. Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D et al (2010) 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(3):466–474. doi:10.1200/jco.2009.23.3452. Epub 2009 Dec 14
4. Tol J, Nagtegaal I, Punt C (2009) BRAF mutation in metastatic colorectal cancer. N Engl J Med 361(1):98–99
5. Yang H, Higgins B, Kolinsky K, Packman K, Bradley WD, Lee RJ et al (2012) Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer. Cancer Res 72(3):779–789
6. Jansen HW, Lurz R, Bister K, Bonner TI, Mark GE, Rapp UR (1984) Homologous cell-derived oncogenes in avian carcinoma virus MH2 and murine sarcoma virus 3611. Nature 307(5948):281–284
7. Sutrave P, Bonner TI, Rapp UR, Jansen HW, Patschinsky T, Bister K (1984) Nucleotide sequence of avian retroviral oncogene v-mil: homologue of murine retroviral oncogene v-raf. Nature 309(5963):85–88
8. Michaloglou C, Vredeveld LC, Mooi WJ, Peeper DS (2008) BRAF(E600) in benign and malignant human tumours. Oncogene 27(7):877–895
9. Chong H, Vikis HG, Guan KL (2003) Mechanisms of regulating the Raf kinase family. Cell Signal 15(5):463–469
10. Schreck R, Rapp UR (2006) Raf kinases: oncogenesis and drug discovery. Int J Cancer 119(10):2261–2271
11. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S et al (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954
12. Fransen K, Klintenas M, Osterstrom A, Dimberg J, Monstein HJ, Soderkvist P (2004) Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis 25(4):527–533
13. Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE (2002) Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418(6901):934
14. Garnett MJ, Marais R (2004) Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6(4):313–319
15. Marchetti A, Felicioni L, Malatesta S, Grazia Sciarrotta M, Guetti L, Chella A et al (2011) Clinical features and outcome of patients with non-small-cell lung cancer harboring BRAF mutations. J Clin Oncol 29(26):3574–3579
16. Cardarella S, Ogino A, Nishino M, Butaney M, Shen J, Lydon C et al (2013) Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res 19(16):4532–4540
17. Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26(22):3279–3290
18. Beeram M, Patnaik A, Rowinsky EK (2005) Raf: a strategic target for therapeutic development against cancer. J Clin Oncol 23(27):6771–6790
19. Roberts PJ, Der CJ (2007) Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26(22):3291–3310
20. Hingorani SR, Jacobetz MA, Robertson GP, Herlyn M, Tuveson DA (2003) Suppression of BRAF(V599E) in human melanoma abrogates transformation. Cancer Res 63(17):5198–5202
21. Sharma A, Trivedi NR, Zimmerman MA, Tuveson DA, Smith CD, Robertson GP (2005) Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors. Cancer Res 65(6):2412–2421
22. Sumimoto H, Hirata K, Yamagata S, Miyoshi H, Miyagishi M, Taira K et al (2006) Effective inhibition of cell growth and invasion of melanoma by combined suppression of BRAF (V599E) and Skp2 with lentiviral RNAi. Int J Cancer 118(2):472–476
23. Lee EJ, Choi C, Park CK, Maeng L, Lee J, Lee A et al (2005) Tracing origin of serrated adenomas with BRAF and KRAS mutations. Virchows Arch 447(3):597–602
24. Chan TL, Zhao W, Leung SY, Yuen ST (2003) BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas. Cancer Res 63(16):4878–4881
25. Italiano A, Hostein I, Soubeyran I, Fabas T, Benchimol D, Evrard S et al (2010) KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: biological and clinical implications. Ann Surg Oncol 17(5):1429–1434
26. Wang L, Cunningham JM, Winters JL, Guenther JC, French AJ, Boardman LA et al (2003) BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res 63(17):5209–5212
27. Oliveira C, Pinto M, Duval A, Brennetot C, Domingo E, Espin E et al (2003) BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency. Oncogene 22(57):9192–9196
28. French AJ, Sargent DJ, Burgart LJ, Foster NR, Kabat BF, Goldberg R et al (2008) Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res 14(11):3408–3415
29. Ogino S, Cantor M, Kawasaki T, Brahmandam M, Kirkner GJ, Weisenberger DJ et al (2006) CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies. Gut 55(7):1000–1006
30. Slattery ML, Curtin K, Sweeney C, Levin TR, Potter J, Wolff RK et al (2007) Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer. Int J Cancer 120(3):656–663
31. Li WQ, Kawakami K, Ruszkiewicz A, Bennett G, Moore J, Iacopetta B (2006) BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status. Mol Cancer 5:2
32. Kambara T, Simms LA, Whitehall VL, Spring KJ, Wynter CV, Walsh MD et al (2004) BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53(8):1137–1144
33. Barault L, Charon-Barra C, Jooste V, de la Vega MF, Martin L, Roignot P et al (2008) Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases. Cancer Res 68(20):8541–8546
34. Weisenberger DJ, Siegmund KD, Campan M, Young J, Long TI, Faasse MA et al (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet 38(7):787–793
35. Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Meyerhardt JA, Loda M et al (2009) CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut 58(1):90–96
36. Veigl ML, Kasturi L, Olechnowicz J, Ma AH, Lutterbaugh JD, Periyasamy S et al (1998) Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci U S A 95(15):8698–8702
37. Jensen LH, Lindebjerg J, Kolvraa S, Cruger DG (2009) Molecular screening for Lynch syndrome: from bench to bedside. J Clin Oncol 27(34):e224, author reply e5
38. Palomaki GE, McClain MR, Melillo S, Hampel HL, Thibodeau SN (2009) EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med 11(1):42–65
39. Ogino S, Brahmandam M, Cantor M, Namgyal C, Kawasaki T, Kirkner G et al (2006) Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component. Mod Pathol 19(1):59–68
40. Naguib A, Mitrou PN, Gay LJ, Cooke JC, Luben RN, Ball RY et al (2010) Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study. BMC Cancer 10:99
41. Leyland-Jones B (2009) Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J Clin Oncol 27(31):5278–5286
42. Tran B, Kopetz S, Tie J, Gibbs P, Jiang ZQ, Lieu CH et al (2011) Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 117(20):4623–4632
43. Assersohn L, Norman A, Cunningham D, Benepal T, Ross PJ, Oates J (1999) Influence of metastatic site as an additional predictor for response and outcome in advanced colorectal carcinoma. Br J Cancer 79(11–12):1800–1805
44. Catalano V, Loupakis F, Graziano F, Torresi U, Bisonni R, Mari D et al (2009) Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy. Br J Cancer 100(6):881–887
45. Richman SD, Seymour MT, Chambers P, Elliott F, Daly CL, Meade AM et al (2009) 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 27(35):5931–5937
46. Bokemeyer C, Kohne C, Rougier P, Stroh C, Schlichting M, Cutsem EV (2010) Cetuximab with chemotherapy (CT) as first-line treatment for metastatic colorectal cancer (mCRC): analysis of the CRYSTAL and OPUS studies according to KRAS and BRAF mutation status. J Clin Oncol 28(15 s):abstr 3506
47. Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M et al (2009) Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 101(3):465–472
48. Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M et al (2012) 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(10):1466–1475
49. Farina-Sarasqueta A, van Lijnschoten G, Moerland E, Creemers GJ, Lemmens VE, Rutten HJ et al (2010) The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol 21(12):2396–2402
50. Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P et al (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26(35):5705–5712
51. Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D et al (2009) KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 101(4):715–721
52. De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G et al (2010) Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy–refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 11(8):753–762
53. Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T et al (2009) Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 27(35):5924–5930
54. Tol J, Dijkstra JR, Klomp M, Teerenstra S, Dommerholt M, Vink-Borger ME et al (2010) Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer 46(11):1997–2009
55. Theodoropoulos GE, Karafoka E, Papailiou JG, Stamopoulos P, Zambirinis CP, Bramis K et al (2009) P53 and EGFR expression in colorectal cancer: a reappraisal of ‘old’ tissue markers in patients with long follow-up. Anticancer Res 29(2):785–791
56. McKay JA, Murray LJ, Curran S, Ross VG, Clark C, Murray GI et al (2002) Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer 38(17):2258–2264
57. Nagasaka T, Sasamoto H, Notohara K, Cullings HM, Takeda M, Kimura K et al (2004) Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J Clin Oncol 22(22):4584–4594
58. Solit DB, Garraway LA, Pratilas CA, Sawai A, Getz G, Basso A et al (2006) BRAF mutation predicts sensitivity to MEK inhibition. Nature 439(7074):358–362
59. Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D et al (2012) Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483(7387):100–103
60. Flaherty K, Puzanov I, Sosman J, Kim K, Ribas A, McArthur G, et al. (2009) Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J Clin Oncol (suppl; abstr 9000) 27:15 s
61. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516
62. Kopetz S, Desai J, Chan E, Hecht JR, O’Dwyer PJ, Lee RJ, et al. (2010) PLX4032 in metastatic colorectal cancer patients with mutant BRAF tumors. J Clin Oncol 28(15 s):suppl; abstr 3534
63. Corcoran RB, Ebi H, Turke AB, Coffee EM, Nishino M, Cogdill AP et al (2012) EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov 2(3):227–235
64. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N (2010) RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 464(7287):427–430
65. Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R et al (2010) RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 464(7287):431–435
66. Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N et al (2010) Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 140(2):209–221
67. Mao M, Tian F, Mariadason JM, Tsao CC, Lemos R Jr, Dayyani F et al (2013) Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents. Clin Cancer Res 19(3):657–667
68. Coffee EM, Faber AC, Roper J, Sinnamon MJ, Goel G, Keung L et al (2013) Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer. Clin Cancer Res 19(10):2688–2698
69. Yuan TL, Cantley LC (2008) PI3K pathway alterations in cancer: variations on a theme. Oncogene 27(41):5497–5510
70. Parsons DW, Wang TL, Samuels Y, Bardelli A, Cummins JM, DeLong L et al (2005) Colorectal cancer: mutations in a signalling pathway. Nature 436(7052):792
71. Bamford S, Dawson E, Forbes S, Clements J, Pettett R, Dogan A et al (2004) The COSMIC (catalogue of somatic mutations in cancer) database and website. Br J Cancer 91(2):355–358
72. Ogino S, Nosho K, Kirkner GJ, Shima K, Irahara N, Kure S et al (2009) PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer. J Clin Oncol 27(9):1477–1484
73. Early Breast Cancer Trialists’ Collaborative Group (1988) Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. An overview of 61 randomized trials among 28,896 women. N Engl J Med 319(26):1681–1692
74. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792
75. Sequist LV, Martins RG, Spigel D, Grunberg SM, Spira A, Janne PA et al (2008) First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 26(15):2442–2449
76. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ et al (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634
77. Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF et al (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66(8):3992–3995
78. Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359(17):1757–1765