Forcing cancer cells to commit suicide

Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms, carcinogenic process, and response of cancer cells to anticancer drugs. It is a genetically strictly regulated process, controlled by the balance between pro- and antiapoptotic proteins. Resistance to standard chemotherapeutics also seems to be an apoptosis-related process due to failure to activate the apoptotic machinery. Hence, the molecular pathways (extrinsic and intrinsic) regulating the apoptotic process are attractive targets for potential therapeutic intervention. The goal of proapoptotic drugs is to selectively induce apoptosis in the tumor cell while leaving healthy cells unharmed. Several proapoptotic receptor agonists have recently been developed, activating selectively the extrinsic pathway, and give promising results. Targets for the intrinsic pathway include the Bcl-2 family proteins, the inhibitor of apoptosis proteins, the p53 pathway, and many others. However, several studies have implicated that using monotherapy will probably not be sufficient to sensitize or induce apoptosis in all tumor cells. Most promising results, in terms of killing the tumor cell, will be achieved by the combination of various therapeutic strategies. In this review, promising apoptosis-inducing anticancer therapies are summarized.