Apoptosis and cancer chemotherapy

Apoptosis is a fundamental mechanism of cell death that can be engaged by a range of cellular insults. One of the major modes of action of chemotherap eutic drugs may be via the activation of apoptosis. Understanding how the c ell death program is engaged following an insult, and hence why it fails to be engaged in certain settings, offers a novel approach to overcoming the clinical problem of drug resistance. The tumour suppressor gene p53 and its downstream effector genes p21, mdm-2,and gadd45 seem to be important in th e cellular response to genotoxic drug induced damage. Considerable evidence has accrued about the effect of mutations of this pathway on drug sensitiv ity and this is discussed. The expanding Bcl-2 family of proteins also play an important role in the cell death program. Evidence suggests that these proteins may function as integrators of damage signals, and may be the fina l decision point as to whether a cell lives or dies. These proteins may thu s represent a logical target for new approaches to overcoming drug resistan ce.