Perspective: The Chemotherapeutic Relevance of Apoptosis and a Proposed Biochemical Cascade for Chemotherapeutically Induced Apoptosis

Abstract

Cancer cells that are sufficiently damaged by cancer chemotherapeutic agents (as well as radiotherapy) eventually die in an ordered sequential biochemical process known as apoptosis. Apoptosis is a general physiological mechanism for controlled cell deletion that is an active (i.e., an energy-dependent, at least initially), inherent (gene-directed) program of cell death, and therefore sometimes referred to as cell suicide and programmed cell death (1,2). The apoptotic biochemical events occurring after the anticancer agent's interaction with its biochemical target is the actual process of cell death and is a secondary phenomenon following the primary drug-target interaction. Thus, anticancer agents, despite having different primary biochemical targets (e.g., inhibition of thymidylate synthase, microtubule damage, topoisomerase inhibitors, DNA crosslinking agents, etc.), all ultimately kill by inducing the biochemical cascade of apoptosis (3,4). However, there is a “qualitative” and “quantitative” heterogeneity in a neoplastic cell population. “Qualitative” heterogeneity establishes the absolute need for a combination of drugs with different biochemical actions to kill all the different subpopulations of malignant cells within the tumor in order to achieve cure.