The mitogen-activated protein kinase pathway in melanoma part I – Activation and primary resistance mechanisms to BRAF inhibition

European Journal of Cancer

Volumn 73, Issue , 2017, Pages 85-92

  Amaral, Teresa ^a,b   Sinnberg, Tobias ^a   Meier, Friedegund ^c   Krepler, Clemens ^d   Levesque, Mitchell ^e   Niessner, Heike ^a   Garbe, Claus ^a  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b Portuguese Air Force Health Direction   (Portugal)

^c UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^d WISTAR INSTITUTE   (United States)

^e UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

BRAF mutation; MAP kinase pathway; Metastatic melanoma; PI3K pathway; Primary resistance to targeted therapy

Indexed keywords

B RAF KINASE INHIBITOR; CYCLIN D1; CYCLIN DEPENDENT KINASE 4; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE INHIBITOR; NEUROFIBROMIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN TYROSINE KINASE; RAC1 PROTEIN; SCATTER FACTOR; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR HOXD8; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; B RAF KINASE; PROTEIN KINASE INHIBITOR;

BENIGN NEOPLASM; CANCER RESISTANCE; COPY NUMBER VARIATION; CROSS RESISTANCE; GENE MUTATION; HUMAN; MELANOMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; DRUG RESISTANCE; GENETICS; MOLECULARLY TARGETED THERAPY; MUTATION; PHYSIOLOGY; PROCEDURES;

ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; HUMANS; MAP KINASE SIGNALING SYSTEM; MELANOMA; MOLECULAR TARGETED THERAPY; MUTATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF;

EID: 85011321309     PISSN: 09598049     EISSN: 18790852     Source Type: Journal    
DOI: 10.1016/j.ejca.2016.12.010     Document Type: Review

References (56)

1. [1] Pearson, G., Robinson, F., Gibson, T.B., Xu, B-e, Karandikar, M., Berman, K., et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22 (2001), 153–183.
2. [2] Garnett, M.J., Rana, S., Paterson, H., Barford, D., Marais, R., Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization. Mol Cell 20 (2005), 963–969.
3. [3] Terai, K., Matsuda, M., The amino-terminal B-Raf-specific region mediates calcium-dependent homo- and hetero-dimerization of Raf. EMBO J 25 (2006), 3556–3564.
4. [4] Shain, A.H., Yeh, I., Kovalyshyn, I., Sriharan, A., Talevich, E., Gagnon, A., et al. The genetic evolution of melanoma from precursor lesions. N Engl J Med 373 (2015), 1926–1936.
5. [5] Lito, P., Pratilas, C.A., Joseph, E.W., Tadi, M., Halilovic, E., Zubrowski, M., et al. Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell 22 (2012), 668–682.
6. [6] Shi, H., Hugo, W., Kong, X., Hong, A., Koya, R.C., Moriceau, G., et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov 4 (2014), 80–93.
7. [7] Trunzer, K., Pavlick, A.C., Schuchter, L., Gonzalez, R., McArthur, G.A., Hutson, T.E., et al. Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol 31 (2013), 1767–1774.
8. [8] Ribas, A., Gonzalez, R., Pavlick, A., Hamid, O., Gajewski, T.F., Daud, A., et al. Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study. Lancet Oncol 15 (2014), 954–965.
9. [9] Larkin, J., Ascierto, P.A., Dreno, B., Atkinson, V., Liszkay, G., Maio, M., et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 371 (2014), 1867–1876.
10. [10] Long, G.V., Stroyakovskiy, D., Gogas, H., Levchenko, E., de Braud, F., Larkin, J., et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 371 (2014), 1877–1888.
11. [11] Robert, C., Karaszewska, B., Schachter, J., Rutkowski, P., Mackiewicz, A., Stroiakovski, D., et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 372 (2015), 30–39.
12. [12] Sullivan, R., Weber, J., Patel, S., A phase Ib/II study of BRAF inhibitor (BRAFi) encorafenib (ENCO) plus MEK inhibitor (MEKi) binimetinib (BINI) in cutaneous melanoma patients naive to BRAFi treatment. J Clin Oncol, 33, 2015 (suppl; abstr 9007). 2015.
13. [13] Menzies, A.M., Wilmott, J.S., Drummond, M., Lo, S., Lyle, M., Chan, M.M.K., et al. Clinicopathologic features associated with efficacy and long-term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors. Cancer 121 (2015), 3826–3835.
14. [14] Flaherty K, Davies MA, Grob JJ, Long GV, Nathan PD, Ribas A, et al. Genomic analysis and 3-y efficacy and safety update of COMBI-d: a Phase III study of dabrafenib (D) + trametinib (T) vs D monotherapy in patients with unresectable or metastatic BRAF V600E/K-mutant cutaneous melanoma. Program and abstracts of the 2016 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2016, Abstract 9502. 2016.
15. [15] Lin, J., Takata, M., Murata, H., Goto, Y., Kido, K., Ferrone, S., et al. Polyclonality of BRAF mutations in acquired melanocytic nevi. J Natl Cancer Inst 101 (2009), 1423–1427.
16. [16] Birchmeier, C., Birchmeier, W., Gherardi, E., Vande Woude, G.F., Met, metastasis, motility and more. Nat Rev Mol Cell Biol 4 (2003), 915–925.
17. [17] Furge, K.A., Zhang, Y.W., Vande Woude, G.F., Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene 19 (2000), 5582–5589.
18. [18] Organ, S.L., Tsao, M.-S., An overview of the c-MET signaling pathway. Ther Adv Med Oncol 3 (2011), S7–S19.
19. [19] Delitto, D., Vertes-George, E., Hughes, S.J., Behrns, K.E., Trevino, J.G., c-Met signaling in the development of tumorigenesis and chemoresistance: potential applications in pancreatic cancer. World J Gastroenterol 20 (2014), 8458–8470.
20. [20] Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z.R., Du, J., et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487 (2012), 500–504.
21. [21] Wilson, T.R., Fridlyand, J., Yan, Y., Penuel, E., Burton, L., Chan, E., et al. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 487 (2012), 505–509.
22. [22] Krepler, C., Xiao, M., Sproesser, K., Brafford, P.A., Shannan, B., Beqiri, M., et al. Personalized preclinical trials in BRAF inhibitor-resistant patient-derived xenograft models identify second-line combination therapies. Clin Cancer Res 22 (2016), 1592–1602.
23. [23] Valentinis, B., Baserga, R., IGF-I receptor signalling in transformation and differentiation. Mol Pathol 54 (2001), 133–137.
24. [24] Hartog, H., Wesseling, J., Boezen, H.M., van der Graaf, W.T.A., The insulin-like growth factor 1 receptor in cancer: old focus, new future. Eur J Cancer 43 (2007), 1895–1904.
25. [25] Baserga, R., Resnicoff, M., Dews, M., The IGF-I receptor and cancer. Endocrine 7 (1997), 99–102.
26. [26] LeRoith, D., Roberts, C.T. Jr., The insulin-like growth factor system and cancer. Cancer Lett 195 (2003), 127–137.
27. [27] Karasic, T.B., Hei, T.K., Ivanov, V.N., Disruption of IGF-1R signaling increases TRAIL-induced apoptosis: a new potential therapy for the treatment of melanoma. Exp Cell Res 316 (2010), 1994–2007.
28. [28] Johannessen, C.M., Boehm, J.S., Kim, S.Y., Thomas, S.R., Wardwell, L., Johnson, L.A., et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468 (2010), 968–972.
29. [29] Gowrishankar, K., Snoyman, S., Pupo, G.M., Becker, T.M., Kefford, R.F., Rizos, H., Acquired resistance to BRAF inhibition can confer cross-resistance to combined BRAF/MEK inhibition. J Invest Dermatol 132 (2012), 1850–1859.
30. [30] Monsma, D.J., Cherba, D.M., Eugster, E.E., Dylewski, D.L., Davidson, P.T., Peterson, C.A., et al. Melanoma patient derived xenografts acquire distinct vemurafenib resistance mechanisms. Am J Cancer Res 5 (2015), 1507–1518.
31. [31] Rizos, H., Menzies, A.M., Pupo, G.M., Carlino, M.S., Fung, C., Hyman, J., et al. BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact. Clin Cancer Res 20 (2014), 1965–1977.
32. [32] Whittaker, S.R., Theurillat, J.P., Van Allen, E., Wagle, N., Hsiao, J., Cowley, G.S., et al. A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. Cancer Discov 3 (2013), 350–362.
33. [33] Gibney, G.T., Smalley, K.S., An unholy alliance: cooperation between BRAF and NF1 in melanoma development and BRAF inhibitor resistance. Cancer Discov 3 (2013), 260–263.
34. [34] Nissan, M.H., Pratilas, C.A., Jones, A.M., Ramirez, R., Won, H., Liu, C., et al. Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence. Cancer Res 74 (2014), 2340–2350.
35. [35] Shalem, O., Sanjana, N.E., Hartenian, E., Shi, X., Scott, D.A., Mikkelsen, T.S., et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343 (2014), 84–87.
36. [36] Maertens, O., Johnson, B., Hollstein, P., Frederick, D.T., Cooper, Z.A., Messiaen, L., et al. Elucidating distinct roles for NF1 in melanomagenesis. Cancer Discov 3 (2013), 338–349.
37. [37] Stark, M.S., Bonazzi, V.F., Boyle, G.M., Palmer, J.M., Symmons, J., Lanagan, C.M., et al. miR-514a regulates the tumour suppressor NF1 and modulates BRAFi sensitivity in melanoma. Oncotarget 6 (2015), 17753–17763.
38. [38] Lassegue, B., San Martin, A., Griendling, K.K., Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circulation Res 110 (2012), 1364–1390.
39. [39] Michaelson, D., Abidi, W., Guardavaccaro, D., Zhou, M., Ahearn, I., Pagano, M., et al. Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division. J Cell Biol 181 (2008), 485–496.
40. [40] Gastonguay, A., Berg, T., Hauser, A.D., Schuld, N., Lorimer, E., Williams, C.L., The role of Rac1 in the regulation of NF-kappaB activity, cell proliferation, and cell migration in non-small cell lung carcinoma. Cancer Biol Ther 13 (2012), 647–656.
41. [41] Hodis, E., Watson, I.R., Kryukov, G.V., Arold, S.T., Imielinski, M., Theurillat, J.P., et al. A landscape of driver mutations in melanoma. Cell 150 (2012), 251–263.
42. [42] Krauthammer, M., Kong, Y., Ha, B.H., Evans, P., Bacchiocchi, A., McCusker, J.P., et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet 44 (2012), 1006–1014.
43. [43] Paraiso, K.H., Xiang, Y., Rebecca, V.W., Abel, E.V., Chen, Y.A., Munko, A.C., et al. PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression. Cancer Res 71 (2011), 2750–2760.
44. [44] Faber, A.C., Corcoran, R.B., Ebi, H., Sequist, L.V., Waltman, B.A., Chung, E., et al. BIM expression in treatment-naive cancers predicts responsiveness to kinase inhibitors. Cancer Discov 1 (2011), 352–365.
45. [45] Xing, F., Persaud, Y., Pratilas, C.A., Taylor, B.S., Janakiraman, M., She, Q.B., et al. Concurrent loss of the PTEN and RB1 tumor suppressors attenuates RAF dependence in melanomas harboring (V600E)BRAF. Oncogene 31 (2012), 446–457.
46. [46] Krepler, C., Xiao, M., Samanta, M., Vultur, A., Chen, H.Y., Brafford, P., et al. Targeting Notch enhances the efficacy of ERK inhibitors in BRAF-V600E melanoma. Oncotarget, 7(44), 2016.
47. [47] Nathanson, K.L., Martin, A.M., Wubbenhorst, B., Greshock, J., Letrero, R., D'Andrea, K., et al. Tumor genetic analyses of patients with metastatic melanoma treated with the BRAF inhibitor dabrafenib (GSK2118436). Clin Cancer Res 19 (2013), 4868–4878.
48. [48] Falchook, G.S., Long, G.V., Kurzrock, R., Kim, K.B., Arkenau, T.H., Brown, M.P., et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 379 (2012), 1893–1901.
49. [49] Sherr, C.J., Roberts, J.M., CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13 (1999), 1501–1512.
50. [50] Flaherty K. Genomic analysis and 3-y efficacy and safety update of COMBI-d: a phase 3 study of dabrafenib (D) + trametinib (T) vs D monotherapy in patients (pts) with unresectable or metastatic BRAF V600E/K-mutant cutaneous melanoma. Presentation: June 3, 2016 Program and abstracts of the 2016 Annual Meeting of the American Society of Clinical Oncology; June 3–7, 2016 Acessed in 19th September 2016. 2016.
51. [51] Smalley, K.S., Lioni, M., Dalla Palma, M., Xiao, M., Desai, B., Egyhazi, S., et al. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol Cancer Ther 7 (2008), 2876–2883.
52. [52] Spitz, F., Gonzalez, F., Peichel, C., Vogt, T.F., Duboule, D., Zákány, J., Large scale transgenic and cluster deletion analysis of the HoxD complex separate an ancestral regulatory module from evolutionary innovations. Genes Dev 15 (2001), 2209–2214.
53. [53] Shinawi, T., Hill, V.K., Krex, D., Schackert, G., Gentle, D., Morris, M.R., et al. DNA methylation profiles of long- and short-term glioblastoma survivors. Epigenetics 8 (2013), 149–156.
54. [54] Leshchenko, V.V., Kuo, P.Y., Shaknovich, R., Yang, D.T., Gellen, T., Petrich, A., et al. Genomewide DNA methylation analysis reveals novel targets for drug development in mantle cell lymphoma. Blood 116 (2010), 1025–1034.
55. [55] Van Allen, E.M., Wagle, N., Sucker, A., Treacy, D.J., Johannessen, C.M., Goetz, E.M., et al. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 4 (2014), 94–109.
56. [56] Penna, I., Molla, A., Grazia, G., Cleris, L., Nicolini, G., Perrone, F., et al. Primary cross-resistance to BRAFV600E-, MEK1/2- and PI3K/mTOR-specific inhibitors in BRAF-mutant melanoma cells counteracted by dual pathway blockade. Oncotarget 7 (2016), 3947–3965.