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Review: Therapeutic opportunities in noncutaneous melanoma

Mount Vernon Cancer Centre - Medical Oncology, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK, nathan.pd{at}gmail.com

P.D. Nathan

Medical Oncology, Mount Vernon Cancer Centre - Medical Oncology, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK

Recent evidence suggests that the biology of noncutaneous melanoma differs significantly from cutaneous melanoma and may provide therapeutic opportunity. The most frequent sites of origin of noncutaneous melanoma are the eye and mucosal surfaces. Although noncutaneous melanomas are an uncommon group of cancers (representing less than 10% of all melanomas) a greater understanding of their genetic and molecular abnormalites is being translated into novel treatment strategies. These developments are important because there is currently no effective systemic therapy for noncutaneous melanoma. Significant attention has been focused on the role of c-kit (KIT, CD117), a transmembrane receptor with tyrosine kinase activity. In vitro and ex vivo evidence suggests that c-kit is frequently expressed/over expressed/mutated in noncutaneous melanoma. Anti-tumour effects with c-kit inhibitors are seen in pre-clinical models. A variety of multitargeted kinase inhibitors which have activity against c-kit are currently in early phase clinical trials in metastatic ocular, mucosal and acral melanoma. The few case reports of significant clinical activity with targeted therapies provides hope that greater understanding of the biology of noncutaneous melanoma can be translated into effective treatment.

Key Words: melanoma • noncutaneous • uveal • mucosal • c-kit • imatinib

References

• Ashida, A., Takata, M., Murata, H., Kido, K. and Saida, T. (2009) Pathological activation of KIT in metastatic tumours of acral and mucosal melanomas. Int J Cancer 124: 862-868.
• Beadling, C., Jacobson-Dunlop, E., Hodi, F.S., Le, C., Warrick, A., Patterson, J. et al. (2008) KIT Gene Mutations and Copy Number in Melanoma Subtypes. Clin Cancer Res 14: 6821-6828.[Abstract/Free Full Text]
• Chan, K.R., Gundala, S., Laudadio, M., Mastrangelo, M., Yamamoto, A. and Sato, T. (2008) A pilot study using sunitinib malate as therapy in patients with stage IV uveal melanoma. J Clin Oncol (suppl 20) 26: abstract 9047.
• Chang, A.E., Karnell, L.H. and Menck, H.R. (1998) The National Cancer Data Base report on cutaneous and noncutaneous melanoma. A summary of 84,836 cases from the past decade. Cancer 83: 1664-1678.[CrossRef][Medline] [Order article via Infotrieve]
• Corrie, P.G., Shaw, J., Spanswick, V.J., Sehmbi, R., Jonson, A., Mayer, A. et al. (2005) Phase I trial combining gemcitabine and treosulfan in advanced cutaneous and uveal melanoma patients. British Journal of Cancer 92: 1997-2003.[CrossRef][Medline] [Order article via Infotrieve]
• Curtin, J.A., Fridlyand, J., Kageshita, T., Patel, H.N., Busam, K.J., Kutzner, H. et al. (2005) Distinct Sets of Genetic Alterations in Melanoma. N Engl J Med 353: 2135-2147.[Abstract/Free Full Text]
• Curtin, J.A., Busam, K., Pinkel, D. and Bastian, B.C. (2006) Somatic Activation of KIT in Distinct Subtypes of Melanoma. J Clin Oncol 24: 4340-4346.[Abstract/Free Full Text]
• Damato, B., Duke, C., Coupland, S.E., Hiscott, P., Smith, P.A., Campbell, I. et al. (2007) Cytogenetics of Uveal Melanoma: A 7-Year Clinical Experience. Ophthalmology 114: 1925-1931.[CrossRef][Medline] [Order article via Infotrieve]
• Hodi, F.S., Friedlander, P., Corless, C.L., Heinrich, M.C., Mac Rae, S., Kruse, A. et al. (2008) Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol 26: 2046-2051.[Free Full Text]
• Hofmann, U.B., Kauczok-Vetter, C.S., Houben, R. and Becker, J.C. (2009) Overexpression of the KIT/ SCF in uveal melanoma does not translate into clinical efficacy of imatinib mesylate. Clin Cancer Res 15: 324-329.
• Isozaki, K., Terris, B., Belghiti, J., Schiffmann, S., Hirota, S. and Vanderwinden, J.M. (2000) Germlineactivating mutation in the kinase domain of KIT gene in familial gastrointestinal stromal tumors. Am J Pathol 157: 1581-1585.[Abstract/Free Full Text]
• Jiang, X., Zhou, J., Yuen, N.K., Corless, C.L., Heinrich, M.C., Fletcher, J.A. et al. (2008) Imatinib targeting of KIT-mutant oncoprotein in melanoma. Clin Cancer Res 14: 7726-7732.[Abstract/Free Full Text]
• Kim, K.B., Eton, O., Davis, D.W., Frazier, M.L., McConkey, D.J., Diwan, A.H. et al. (2008) Phase II trial of imatinib mesylate in patients with metastatic melanoma. Br J Cancer 99: 734-740.[CrossRef][Medline] [Order article via Infotrieve]
• Kivelaä, T., Suciu, S., Hansson, J., Kruit, W.H., Vuoristo, M.S., Kloke, O. et al. (2003) Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur J Cancer 39: 1115-1120.[CrossRef][Medline] [Order article via Infotrieve]
• Lefevre, G., Glotin, A.L., Calipel, A., Mouriaux, F., Tran, T., Kherrouche, Z. et al. (2004) Roles of stem cell factor/c-Kit and effects of Glivec/STI571 in human uveal melanoma cell tumorigenesis. J Biol Chem 279: 31769-31779.[Abstract/Free Full Text]
• Lutzky, J., Bauer, J. and Bastian, B.C. (2008) Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation. Pigment Cell Melanoma Res 21: 492-493.[CrossRef][Medline] [Order article via Infotrieve]
• Mouriaux, F., Kherrouche, Z., Maurage, C.A., Demailly, F.X., Labalette, P. and Saule, S. (2003) Expression of the c-kit receptor in choroidal melanomas. Melanoma Res 13: 161-166.[CrossRef][Medline] [Order article via Infotrieve]
• Penel, N., Delcambre, C., Durando, X., Clisant, S., Hebbar, M., Negrier, S. et al. (2008) O-Mel-Inib: a Cancéro-pôle Nord-Ouest multicenter phase II trial of high-dose imatinib mesylate in metastatic uveal melanoma. Invest New Drugs 26: 561-565.[CrossRef][Medline] [Order article via Infotrieve]
• Schmittel, A., Schmidt-Hieber, M., Martus, P., Bechrakis, N.E., Schuster, R., Siehl, J.M. et al. (2006) A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma. Ann Oncol 17: 1826-1829.[Abstract/Free Full Text]
• Shah, C.P., Weism, E., Lajous, M., Shields, J.A. and Shields, C.L. (2005) Intermittent and chronic ultraviolet light exposure and uveal melanoma: a meta-analysis. Ophthalmology 112: 1599-1607.[CrossRef][Medline] [Order article via Infotrieve]
• Singh, A.D., De Potter, P., Fijal, B.A., Shields, C.L., Shields, J.A. and Elston, R.C. (1998) Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis. Ophthalmology 105: 195-198.[CrossRef][Medline] [Order article via Infotrieve]
• Steinberg, M. (2007) Dasatinib: a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia. Clin Ther 29: 2289-2308.[CrossRef][Medline] [Order article via Infotrieve]
• Van Raamsdonk, C.D., Bezrookove, V., Green, G., Bauer, J., Gaugler, L., O'Brien, J.M. et al. (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457: 599-602.[CrossRef][Medline] [Order article via Infotrieve]
• Virgili, G., Gatta, G., Ciccolallo, L., Capocaccia, R., Biggeri, A., Crocetti, E. et al. (2007) Incidence of uveal melanoma in Europe. Ophthalmology 114: 2309-2315.[CrossRef][Medline] [Order article via Infotrieve]
• Weis, E., Shah, C.P., Lajous, M., Shields, J.A. and Shields, C.L. (2006) The association between host susceptibility factors and uveal melanoma: a meta-analysis. Arch Ophthalmol 124: 54-60.[Abstract/Free Full Text]
• Weisberg, E., Manley, P.W., Breitenstein, W., Brüggen, J., Cowan-Jacob, S.W. and Ray, A. (2005) Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 7: 129-141.[CrossRef][Medline] [Order article via Infotrieve]

Therapeutic Advances in Medical Oncology, Vol. 1, No. 1, 29-36 (2009)
DOI: 10.1177/1758834009337664


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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Wilkins, D.K. Articles by Nathan, P.D. Social Bookmarking                         What's this?