Modulating sensitivity to drug-induced apoptosis: the future for chemotherapy?

Drug resistance is a fundamental problem in the treatment of most common hu man cancers. Our understanding of the cellular mechanisms underlying death and survival has allowed the development of rational approaches to overcomi ng drug resistance. The mitogen activated protein kinase family of protein serine/threonine kinases has been implicated in this complex web of signall ing, with some members acting to enhance death and other members to prevent it. A recent publication by MacKeigan ef al is the first to demonstrate an enhancement of drug-induced cell death by simultaneous blockade of MEK-med iated survival signalling, and offers the potential for targeted adjuvant t herapy as a means of overcoming drug resistance.