1. ¹Melanoma Program, Department of Dermatology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 28109, USA
2. ²Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

Correspondence: MS Soengas, E-mail: soengas@umich.edu

Abstract

Melanoma is the most aggressive form of skin cancer and is notoriously resistant to all current modalities of cancer therapy. A large set of genetic, functional and biochemical studies suggest that melanoma cells become 'bullet proof' against a variety of chemotherapeutic drugs by exploiting their intrinsic resistance to apoptosis and by reprogramming their proliferation and survival pathways during melanoma progression. In recent years, the identification of molecules involved in the regulation and execution of apoptosis, and their alteration in melanoma, have provided new insights into the molecular basis for melanoma chemoresistance. With this knowledge in hand, the challenge is now to devise strategies potent enough to compensate or bypass these cell death defects and improve the actual poor prognosis of patients at late stages of the disease.