Apoptosis in Cutaneous Melanoma

  • Michael B. Nicholl
  • Dave S.B. Hoon

Abstract

Cutaneous melanoma is in general highly refractory to chemotherapy and radiotherapy. Melanoma has been resistant to therapeutics that induce apoptosis leading to a poor outcome in development of effective therapeutics. Over the years countless experimental drugs have been tested to induce apoptosis to melanoma cells in patients but very few have gone beyond phase III treatment. As melanoma progresses it develops stronger anti-apoptotic properties, thus the management of disease beyond surgical resection is very difficult. In this review we examine some of the key factors that have been shown to play a role relating to anti-apoptosis events in melanoma. These factors include p53, APAF-1 (apoptotic protease activating factor-1), Bcl-2, and IAP (inhibitors of apoptosis). The review presents how several of these factors, such APAF-1 and IAPs, can be used as surrogate biomarkers for disease outcome. APAF-1 loss or downregulation was demonstrated to be an important factor in melanoma’s aggressive behavior. The use of apoptosis related factors as biomarkers can be applied to assess both tumor tissue and blood. By assessing tumors and identifying their potential of resistance to therapeutic intervention, alternative treatment strategies may be considered. Effective therapeutics to melanoma may be developed to target agents that cause apoptosis-independent death. It is highly important to further understand the mechanism of melanoma cell apoptosis resistance in order to develop more effective new therapeutics.

Keywords

APAF-1 Melanoma Survivin Apoptosis IAP 

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Michael B. Nicholl
    • 1
  • Dave S.B. Hoon
    • 2
  1. 1.Department of Molecular OncologyJohn Wayne Cancer Institute, 2200 Santa Monica Boulevard Santa MonicaUSA
  2. 2.Department of Molecular OncologyJohn Wayne Cancer Institute, 2200 Santa Monica Boulevard Santa MonicaUSA

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