The CD95/CD95 ligand (CD95L) system regulates cell death, which plays a relevant role in cancer. The impairment of the
CD95/CD95L system in cancer cells may lead to apoptosis resistance and contributes to tumor progression. However, a complete loss of
CD95 is rarely seen in human cancers, and many cancer cells express large quantities of CD95. Furthermore, cancer patients frequently
have elevated levels of the CD95L, which raise the possibility that CD95 could also participate in tumor growth through its non-apoptotic
activities depending of cell lineages or tumor stage. For this reason, CD95 signaling has to be taken into account in tumor biology, and
the multiple regulatory targets of CD95/CD95L suggest that they may be used as a potential therapeutic strategy to treat cancer. The present
review is an update of anti-CD95-related cancer therapies such as anti-CD95 antibodies, CD95L fusion proteins, CD95 pro-drugs, as
well as the new genetic CD95-based therapies.