Role of Apoptosis in Cancer: War of the Worlds, Therapeutic Targets and Strategies

Evading apoptosis is a pioneer hallmark of all cancers, and cancer therapeutics worldwide mainly focus on activating programmed cell death mechanisms. Various cellular mechanisms involving loss of tumour suppressors, activation of oncogenic growth factors, and epigenetic silencing act as primary anti-apoptotic signals for promoting cancer. The emergence of additional cancer hallmarks in the last decade that bypasses or dampen apoptosis signals, like metabolic reprogramming, immune evasion, phenotypic plasticity, microbiota interactions and epigenetic reprogramming, indicates an arsenal of strategies deployed by this multifaced disease against cell death. Combinatorial therapies are being engaged in clinics to synergise the cell death potentials of these agents. However, with the rise of therapy-resistant cancers and severe side effects of chemotherapy drugs, new strategies are required to treat the disease. The chapter will cover various aspects of cell death and cancer, emphasising apoptotic evasion, mechanism failures, therapy resistance, transcriptional rewiring, and modern combinatorial therapeutic strategies.