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The Oncologist-2004-Perlis-182-7 - The OM C ncologist...

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Recent Advances in Melanoma Biology C LIFF P ERLIS , a M EENHARD H ERLYN b a Department of Dermatology, Brown Medical School, Providence, Rhode Island, USA; b Wistar Institute, Philadelphia, Pennsylvania, USA Key Words. Melanoma · Cell adhesion molecules · Apoptosis · Ultraviolet radiation A BSTRACT The incidence and mortality rates of melanoma have increased at annual rates of 2%-3% for the last 30 years. Disseminated disease is largely refractory to cytotoxic chemotherapy and is almost universally fatal. Several recent advances in melanoma biology offer new strategies for potentially treating this aggres- sive malignancy. This review focuses on three sig- nificant advances involving tumor initiation, etiology, and progression. New experimental models reveal a direct role for UV-B light in initiating melanomas in human skin. Studies on E- and N-cadherin elucidate the importance of local homeostatic mechanisms in regulating tumor progression. Finally, several discov- eries concerning apoptotic mechanisms in melanoma suggest strategies for future treatments. The Oncologist 2004;9:182-187 The Oncologist 2004;9:182-187 www.TheOncologist.com Correspondence: Meenhard Herlyn, D.V.M., D.Sc., The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA. Telephone: 215-898-3959; Fax: 215-898-0980; e-mail: [email protected] Received February 13, 2003; accepted for publication August 27, 2003. ©AlphaMed Press 1083-7159/2003/$12.00/0 I NTRODUCTION The increase in melanoma incidence in U.S. Caucasians is among the greatest for any cancer. From 1973 to 1994, melanoma incidence rates increased 120.5% [1]. It was estimated that 7,400 people in the U.S. would die from melanoma in 2003 [2]. Recent Surveillance, Epidemiology, and End Results (SEER) Program data reveal a 1.91% lifetime risk for Caucasian men to be diag- nosed with melanoma and a 1.37% risk for Caucasian women [3]. In addition to the rising incidence, mortality rates have also increased, though at a slower rate. The mortality rate due to melanoma increased 38.9% from 1973 to 1994 [1]. While early, localized disease is effectively treated with wide excision, metastatic disease is almost universally fatal. The median survival time for patients with disseminated melanoma is 8.1 months with only approximately 2% sur- viving for 5 years [4]. Treatments for advanced disease are inadequate. Chemotherapy with cytotoxic agents has a low cure rate of 1% and significant toxicity. Similar cure rates T he O ncologist ® M elanoma and C utaneous M alignancies L EARNING O BJECTIVES After completing this course, the reader will be able to: 1. Identify the epidemiological evidence supporting the association of intermittent sun exposure with melanoma. 2. Discuss the role of cell adhesion molecules in melanoma progression. 3. List several steps in apoptotic pathways that may prove useful targets for future therapeutic interventions.
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