Apoptosis in Cancer: From Threat to Therapy

Abstract

Apoptosis is a tightly regulated form of programmed cell death essential for tissue homeostasis and genomic integrity. Its dysregulation contributes to diverse pathological conditions, particularly cancer, where evasion of apoptosis enables malignant transformation, tumour progression, immune escape, and therapeutic resistance. Contemporary understanding recognises apoptosis as an integrated network involving mitochondrial, death receptor, and caspase-dependent signalling pathways rather than isolated linear cascades. This review synthesises current insights into the molecular mechanisms governing apoptotic regulation and examines how disruptions in BCL-2 family proteins, p53 signalling, caspase activation, and inhibitor of apoptosis proteins promote carcinogenesis. Particular emphasis is placed on translational advances in apoptosis-targeted therapy, including the clinical success of BH3 mimetics, emerging p53-modulating strategies, and combinational approaches designed to overcome apoptotic resistance. By integrating mechanistic biology with therapeutic development, this review highlights apoptosis not only as a hallmark of cancer but also as a therapeutically exploitable vulnerability in selected cancer contexts, particularly in haematological malignancies, although its translation in solid tumours remains variable and often limited. Understanding tumour-specific apoptotic dependencies may enable more precise and less toxic anticancer strategies in the evolving era of precision oncology.