Apoptosis and therapy

The dogma that antineoplastic treatments kill tumour cells by damaging esse ntial biological functions has been countered by the notion that treatment itself initiates a programmed cellular response. This response often produc es the morphological features of apoptosis and is determined by a network o f proliferation and survival genes, some of which are differentially expres sed in normal and malignant cells. Correspondingly, mutations that interfer e with the initiation or execution of apoptosis may produce tumour-cell dru g resistance. Remarkably, many of the genes that modulate apoptosis in resp onse to cytotoxic drugs also affect apoptosis during tumour development; he nce, the process of apoptosis provides a conceptual framework for understan ding how cancer genes can influence the outcome of cancer therapy. Although the relative contribution of apoptosis to radiation and drug-induced cell death remains controversial, clinical studies have associated anti-apoptoti c mutations with treatment failure. While careful preclinical and clinical studies will be necessary to resolve this point, our current understanding of apoptosis should facilitate the design of rational new therapies. Copyri ght (C) 1999 John Wiley & Sons, Ltd.