Therapeutics Targeting the Core Apoptotic Machinery.

Abstract

Simple SummaryCancer develops when the balance between cell death and cell division in tissues is dysregulated. A key focus of cancer drug discovery is identifying therapeutic agents which will selectively kill and eliminate cancer cells from the body. A number of proteins can prevent the death of cancer cells and developing inhibitors against these proteins to promote cancer cell death is a focus of recent drug discovery efforts. This review aims to summarize the key targets being explored, the drug development approaches being adopted, and the success or limitations of agents currently approved or in clinical development.Therapeutic targeting of the apoptotic pathways for the treatment of cancer is emerging as a valid and exciting approach in anti-cancer therapeutics. Accumulating evidence demonstrates that cancer cells are typically “addicted” to a small number of anti-apoptotic proteins for their survival, and direct targeting of these proteins could provide valuable approaches for directly killing cancer cells. Several approaches and agents are in clinical development targeting either the intrinsic mitochondrial apoptotic pathway or the extrinsic death receptor mediated pathways. In this review, we discuss the main apoptosis pathways and the key molecular targets which are the subject of several drug development approaches, the clinical development of these agents and the emerging resistance factors and combinatorial treatment approaches for this class of agents with existing and emerging novel targeted anti-cancer therapeutics.