Prosurvival and antiapoptotic B cell lymphoma-2 (Bcl-2) family proteins are often overexpressed in cutaneous melanoma, one of the most aggressive types of human cancer. They are also implicated in resistance to therapy and participate in melanoma progression by regulating various processes, including cell proliferation, migration, invasion, and crosstalk with the tumor microenvironment. In this review, we summarize recent findings related to prosurvival members of the Bcl-2 family beyond their canonical functions in the apoptotic pathway, mainly focusing on their potential roles as diagnostic and prognostic biomarkers in cutaneous melanoma. We also provide an overview of different approaches used to inhibit Bcl-2 proteins in preclinical and clinical studies, which are mainly based on the inhibition of protein expression or the disruption of their antiapoptotic functions.
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