Targeted therapy for melanoma: A primer

Surgical Oncology Clinics of North America

Volumn 20, Issue 1, 2011, Pages 165-180

  Davies, Michael A ^a   Gershenwald, Jeffrey E ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

BRAF; C KIT; GN Q; NRAS; PTEN; Targeted therapy

Indexed keywords

ANTINEOPLASTIC AGENT; B RAF KINASE; CARBOPLATIN; G PROTEIN COUPLED RECEPTOR; GSK 2118436; GUANOSINE TRIPHOSPHATASE; MAMMALIAN TARGET OF RAPAMYCIN; NRAS PROTEIN; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PLX 4032; PROTEIN GN ALPHA Q; PROTEIN KINASE B; SORAFENIB; STEM CELL FACTOR; TEMSIROLIMUS; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; CANCER COMBINATION CHEMOTHERAPY; CLINICAL TRIAL; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG TOLERABILITY; ENZYME ACTIVATION; GENE AMPLIFICATION; GENE MUTATION; GENETIC ASSOCIATION; HUMAN; KERATOACANTHOMA; MELANOMA; METASTASIS; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; MUTATIONAL ANALYSIS; NONHUMAN; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SKIN CARCINOMA; SQUAMOUS CELL CARCINOMA; TREATMENT OUTCOME;

DNA PRIMERS; GENE AMPLIFICATION; GENE DELETION; HUMANS; MELANOMA; MUTATION; PHOSPHOTRANSFERASES; PREVALENCE; PROTO-ONCOGENE PROTEINS B-RAF; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-KIT; SIGNAL TRANSDUCTION; SKIN NEOPLASMS; TRANSLATIONAL RESEARCH; UNITED STATES;

EID: 78649506792     PISSN: 10553207     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.soc.2010.09.003     Document Type: Review

References (103)

1. Tsao H., Atkins M.B., Sober A.J. Management of cutaneous melanoma. N Engl J Med 2004, 351(10):998-1012.
2. Atkins M.B., Kunkel L., Sznol M., et al. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am 2000, 6(Suppl 1):S11-14.
3. Phan G.Q., Attia P., Steinberg S.M., et al. Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma. J Clin Oncol 2001, 19(15):3477-3482.
4. Hodi F.S., O 'Day S.J., McDermott D.F., et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010, 363(8):711-723.
5. Atkins M.B., Lotze M.T., Dutcher J.P., et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999, 17(7):2105.
6. Davies M., Hennessy B., Mills G.B. Point mutations of protein kinases and individualised cancer therapy. Expert Opin Pharmacother 2006, 7(16):2243-2261.
7. Mass R.D., Press M.F., Anderson S., et al. Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab. Clin Breast Cancer 2005, 6(3):240-246.
8. Miller A.J., Mihm M.C. Melanoma. N Engl J Med 2006, 355(1):51-65.
9. Curtin J.A., Fridlyand J., Kageshita T., et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005, 353(20):2135-2147.
10. Harbour J.W. Molecular prognostic testing and individualized patient care in uveal melanoma. Am J Ophthalmol 2009, 148(6):823-829. e821.
11. Landreville S., Agapova O.A., Harbour J.W. Emerging insights into the molecular pathogenesis of uveal melanoma. Future Oncol 2008, 4(5):629-636.
12. Colicelli J. Human RAS superfamily proteins and related GTPases. Sci STKE 2004, 2004(250):RE13.
13. Rubinfeld H., Seger R. The ERK cascade: a prototype of MAPK signaling. Mol Biotechnol 2005, 31(2):151-174.
14. Davies H., Bignell G.R., Cox C., et al. Mutations of the BRAF gene in human cancer. Nature 2002, 417(6892):949-954.
15. Hocker T., Tsao H. Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants. Hum Mutat 2007, 28(6):578-588.
16. Pollock P.M., Harper U.L., Hansen K.S., et al. High frequency of BRAF mutations in nevi. Nat Genet 2003, 33(1):19-20.
17. Poynter J.N., Elder J.T., Fullen D.R., et al. BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res 2006, 16(4):267-273.
18. Indsto J.O., Kumar S., Wang L., et al. Low prevalence of RAS-RAF-activating mutations in Spitz melanocytic nevi compared with other melanocytic lesions. J Cutan Pathol 2007, 34(6):448-455.
19. Bauer J., Curtin J.A., Pinkel D., et al. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol 2007, 127(1):179-182.
20. Saldanha G., Purnell D., Fletcher A., et al. High BRAF mutation frequency does not characterize all melanocytic tumor types. Int J Cancer 2004, 111(5):705-710.
21. Garnett M.J., Rana S., Paterson H., et al. Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization. Mol Cell 2005, 20(6):963-969.
22. Heidorn S.J., Milagre C., Whittaker S., et al. Kinase-Dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010, 140(2):209-221.
23. Hingorani S.R., Jacobetz M.A., Robertson G.P., et al. Suppression of BRAF(V599E) in human melanoma abrogates transformation. Cancer Res 2003, 63(17):5198-5202.
24. Sumimoto H., Miyagishi M., Miyoshi H., et al. Inhibition of growth and invasive ability of melanoma by inactivation of mutated BRAF with lentivirus-mediated RNA interference. Oncogene 2004, 23(36):6031-6039.
25. Strumberg D. Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today (Barc) 2005, 41(12):773-784.
26. Karasarides M., Chiloeches A., Hayward R., et al. B-RAF is a therapeutic target in melanoma. Oncogene 2004, 23(37):6292-6298.
27. Eisen T., Ahmad T., Flaherty K.T., et al. Sorafenib in advanced melanoma: a phase II randomised discontinuation trial analysis. Br J Cancer 2006, 95(5):581-586.
28. Flaherty K.T., Schiller J., Schuchter L.M., et al. A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel. Clin Cancer Res 2008, 14(15):4836-4842.
29. Hodi F.S., Soiffer R.J., Clark J., et al. Phase II study of paclitaxel and carboplatin for malignant melanoma. Am J Clin Oncol 2002, 25(3):283-286.
30. Zimpfer-Rechner C., Hofmann U., Figl R., et al. Randomized phase II study of weekly paclitaxel versus paclitaxel and carboplatin as second-line therapy in disseminated melanoma: a multicentre trial of the Dermatologic Co-operative Oncology Group (DeCOG). Melanoma Res 2003, 13(5):531-536.
31. Hauschild A., Agarwala S.S., Trefzer U., et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage iii or stage iv melanoma. J Clin Oncol 2009, 27(17):2823-2830.
32. Dankort D., Curley D.P., Cartlidge R.A., et al. Braf(V600E) cooperates with Pten loss to induce metastatic melanoma. Nat Genet 2009, 41(5):544-552.
33. Michaloglou C., Vredeveld L.C., Soengas M.S., et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 2005, 436(7051):720-724.
34. Patton E.E., Widlund H.R., Kutok J.L., et al. BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr Biol 2005, 15(3):249-254.
35. Escudier B, Szczylik C, Eisen T, et-al. Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). Presented at: ASCO Annual Meeting 2005. Orlando (FL), May 13-17, 2005.
36. Ratain M.J., Eisen T., Stadler W.M., et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006, 24(16):2505-2512.
37. Jilaveanu L., Zito C., Lee S.J., et al. Expression of sorafenib targets in melanoma patients treated with carboplatin, paclitaxel and sorafenib. Clin Cancer Res 2009, 15(3):1076-1085.
38. Tsai J., Lee J.T., Wang W., et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci U S A 2008, 105(8):3041-3046.
39. Yang H., Higgins B., Kolinsky K., et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models. Cancer Res 2010, 70(13):5518-5527.
40. Flaherty K.T., Puzanov J., Sosman J., et al. Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J Clin Oncol 2009, 27(15s):9000.
41. Flaherty K.T., Puzanov I., Kim K.B., et al. Inhibition of mutated, activated braf in metastatic melanoma. N Engl J Med 2010, 363(9):809-819.
42. Kefford R.F., Arkenau H., Brown M.P., et al. Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors. J Clin Oncol 2010, 28(15s):8503.
43. Halaban R., Zhang W., Bacchiocchi A., et al. PLX4032, a selective BRAF V600E kinase inhibitor, activates the erk pathway and enhances cell migration and proliferation of braf wt melanoma cells. Pigment Cell Melanoma Res 2010, 23(2):190-200.
44. Poulikakos P.I., Zhang C., Bollag G., et al. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010, 464(7287):427-430.
45. Hatzivassiliou G., Song K., Yen I., et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 2010, 464(7287):431-435.
46. Smalley K.S., Xiao M., Villanueva J., et al. CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations. Oncogene 2009, 28(1):85-94.
47. Giehl K. Oncogenic Ras in tumour progression and metastasis. Biol Chem 2005, 386(3):193-205.
48. Edlundh-Rose E.A., Egyhazi S.B., Omholt K.B., et al. NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res 2006, 16(6):471-478.
49. Omholt K., Platz A., Kanter L., et al. NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Clin Cancer Res 2003, 9(17):6483-6488.
50. Tsao H., Goel V., Wu H., et al. Genetic interaction between nras and braf mutations and pten//mmac1 inactivation in melanoma. J Invest Dermatol 2004, 122(2):337-341.
51. Bastian B.C., LeBoit P.E., Pinkel D. Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features. Am J Pathol 2000, 157(3):967-972.
52. van Dijk M.C., Bernsen M.R., Ruiter D.J.P. Analysis of mutations in b-raf, n-ras, and h-ras genes in the differential diagnosis of Spitz nevus and spitzoid melanoma. Am J Surg Pathol 2005, 29(9):1145-1151.
53. Greene V.R., Johnson M.M., Grimm E.A., et al. Frequencies of NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma. J Invest Dermatol 2009, 129(6):1483-1488.
54. Dumaz N., Hayward R., Martin J., et al. In Melanoma, RAS mutations are accompanied by switching signaling from BRAF to CRAF and disrupted cyclic AMP Signaling. Cancer Res 2006, 66(19):9483-9491.
55. Konstantinopoulos P.A., Karamouzis M.V., Papavassiliou A.G. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nat Rev Drug Discov 2007, 6(7):541-555.
56. Zhang F.L., Kirschmeier P., Carr D., et al. Characterization of Ha-ras, N-ras, Ki-Ras4A, and Ki-Ras4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type I. J Biol Chem 1997, 272(15):10232-10239.
57. Downward J. PI 3-kinase, Akt and cell survival. Semin Cell Dev Biol 2004, 15(2):177-182.
58. Courtney K.D., Corcoran R.B., Engelman J.A. The PI3K pathway as drug target in human cancer. J Clin Oncol 2010, 28(6):1075-1083.
59. Hennessy B.T., Smith D.L., Ram P.T., et al. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 2005, 4(12):988-1004.
60. Vivanco I., Sawyers C.L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002, 2(7):489-501.
61. Yuan T.L., Cantley L.C. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008, 27(41):5497-5510.
62. Maehama T., Dixon J.E. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 1998, 273(22):13375-13378.
63. Stahl J.M., Cheung M., Sharma A., et al. Loss of PTEN promotes tumor development in malignant melanoma. Cancer Res 2003, 63(11):2881-2890.
64. Mirmohammadsadegh A., Marini A., Nambiar S., et al. Epigenetic silencing of the PTEN gene in melanoma. Cancer Res 2006, 66(13):6546-6552.
65. Wu H., Goel V., Haluska F.G. PTEN signaling pathways in melanoma. Oncogene 2003, 22(20):3113-3122.
66. Zhou X.P., Gimm O., Hampel H., et al. Epigenetic PTEN silencing in malignant melanomas without PTEN mutation. Am J Pathol 2000, 157(4):1123-1128.
67. Goel V.K., Lazar A.J., Warneke C.L., et al. Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma. J Invest Dermatol 2006, 126(1):154-160.
68. Tsao H., Zhang X., Benoit E., et al. Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines. Oncogene 1998, 16(26):3397-3402.
69. Tsao H., Zhang X., Fowlkes K., et al. Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines. Cancer Res 2000, 60(7):1800-1804.
70. Davies M.A., Stemke-Hale K., Lin E., et al. Integrated molecular and clinical analysis of AKT activation in metastatic melanoma. Clin Cancer Res 2009, 15(24):7538-7546.
71. Vasudevan K.M., Barbie D.A., Davies M.A., et al. AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer. Cancer Cell 2009, 16(1):21-32.
72. Omholt K., Krockel D., Ringborg U., et al. Mutations of PIK3CA are rare in cutaneous melanoma. Melanoma Res 2006, 16(2):197-200.
73. Curtin J.A., Stark M.S., Pinkel D., et al. PI3-kinase subunits are infrequent somatic targets in melanoma. J Invest Dermatol 2006, 126(7):1660-1663.
74. Carpten J.D., Faber A.L., Horn C., et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 2007, 448(7152):439-444.
75. Davies M.A., Stemke-Hale K., Tellez C., et al. A novel AKT3 mutation in melanoma tumours and cell lines. Br J Cancer 2008, 99(8):1265-1268.
76. Robertson G.P. Functional and therapeutic significance of Akt deregulation in malignant melanoma. Cancer Metastasis Rev 2005, 24(2):273-285.
77. Stahl J.M., Sharma A., Cheung M., et al. Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res 2004, 64(19):7002-7010.
78. Margolin K., Longmate J., Baratta T., et al. CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium. Cancer 2005, 104(5):1045-1048.
79. Kim K.B., Davies M.A., Papadopoulos N., et al. Phase I/II study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma. J Clin Oncol 2009, 27(15s):9026.
80. Tabernero J., Rojo F., Calvo E., et al. Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol 2008, 26(10):1603-1610.
81. O 'Reilly K.E., Rojo F., She Q.B., et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006, 66(3):1500-1508.
82. Sarbassov D.D., Ali S.M., Sengupta S., et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006, 22(2):159-168.
83. Chresta C.M., Davies B.R., Hickson I., et al. AZD8055 Is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res 2010, 70(1):288-298.
84. Engelman J.A., Chen L., Tan X., et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008, 14(12):1351-1356.
85. Jaiswal B.S., Janakiraman V., Kljavin N.M., et al. Combined targeting of BRAF and CRAF or BRAF and PI3K effector pathways is required for efficacy in NRAS mutant tumors. PLoS One 2009, 4(5):e5717.
86. Tran M.A., Gowda R., Sharma A., et al. Targeting V600EB-Raf and Akt3 using nanoliposomal-small interfering RNA inhibits cutaneous melanocytic lesion development. Cancer Res 2008, 68(18):7638-7649.
87. Curtin J.A., Busam K., Pinkel D., et al. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 2006, 24(26):4340-4346.
88. Beadling C., Jacobson-Dunlop E., Hodi F.S., et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res 2008, 14(21):6821-6828.
89. Handolias D., Salemi R., Murray W., et al. Mutations in KIT occur at low frequency in melanomas arising from anatomical sites associated with chronic and intermittent sun exposure. Pigment Cell Melanoma Res 2010, 23:210-215.
90. Woodman S.E., Davies M.A. Targeting KIT in melanoma: a paradigm of molecular medicine and targeted therapeutics. Biochem Pharmacol 2010, 80(5):568-574.
91. Hirota S., Isozaki K., Moriyama Y., et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998, 279(5350):577-580.
92. Blanke C.D., Demetri G.D., von Mehren M., et al. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol 2008, 26(4):620-625.
93. Demetri G.D., von Mehren M., Blanke C.D., et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002, 347(7):472-480.
94. Huang S., Luca M., Gutman M., et al. Enforced c-KIT expression renders highly metastatic human melanoma cells susceptible to stem cell factor-induced apoptosis and inhibits their tumorigenic and metastatic potential. Oncogene 1996, 13(11):2339-2347.
95. Hodi F.S., Friedlander P., Corless C.L., et al. Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol 2008, 26(12):2046-2051.
96. Woodman S.E., Trent J.C., Stemke-Hale K., et al. Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates. Mol Cancer Ther 2009, 8(8):2079-2085.
97. Quintas-Cardama A., Lazar A.J., Woodman S.E., et al. Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib. Nat Clin Pract Oncol 2008, 5(12):737-740.
98. Onken M.D., Worley L.A., Long M.D., et al. Oncogenic mutations in GNAQ occur early in uveal melanoma. Invest Ophthalmol Vis Sci 2008, 49(12):5230-5234.
99. Van Raamsdonk C.D., Bezrookove V., Green G., et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 2009, 457(7229):599-602.
100. Boni A., Cogdill A.P., Dang P., et al. Selective BRAFV600E inhibition enhances T-Cell recognition of melanoma without affecting lymphocyte function. Cancer Res 2010, 70(13):5213-5219.
101. López-Fauqued M., Gil R., Grueso J., et al. The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. Int J Cancer 2010, 126(7):1549-1561.
102. Pleasance E.D., Cheetham R.K., Stephens P.J., et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010, 463(7278):191-196.
103. Prickett T.D., Agrawal N.S., Wei X., et al. Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat Genet 2009, 41(10):1127-1132.