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Inactivation of apoptosis is the prime phenomenon in cancer development and cancer treatments. Mutations in the apoptotic pathway not only exert resistance to apoptosis and provide a survival advantage to cancer cells but also confer resistance to cancer therapies. Escaping apoptosis is the “hallmark” of cancer cells. Cancer cells can withstand many apoptotic stimuli, such as DNA damage, unfavorable environments, and cytotoxic therapies. Substantial research has been carried out and is in good progress on the various mechanisms adopted by cancer cells to evade apoptosis. This article reviews the apoptosis escape mechanisms by cancer cells, viz. apoptotic gene alterations (in few essential and accessory apoptotic genes), post-translational modifications (phosphorylation and ubiquitination of apoptotic proteins), metabolic alterations, mitochondrial alterations, immunity escape, epigenetics, cancer cell dormancy, cancer clonal theory, and reversibility of apoptosis. The review reveals that there is a wide scope for further research to address the various challenges in realizing successful cancer therapies that involve reversing the apoptotic resistance and/or inducing apoptosis in tumor cells.

Mechanisms adopted by cancer cells to escape apoptosis–A review