Signal transduction therapy targeting apoptosis pathways in cancers

Apoptosis, the cell's intrinsic death program, is a key regulator of tissue homeostasis. Thus, any imbalance between cell death and proliferation may favor tumor formation. Moreover, killing of cancer cells by cytotoxic therapies currently used in clinical oncology such as chemotherapy or gamma-irradiation is primarily mediated by triggering apoptosis as well as other forms of cell death in cancer cells. Accordingly, defects in apoptosis pathways may lead to cancer resistance. Understanding the molecular pathways that regulate apoptosis in different types of malignancies and how resistant cancer cells successfully evade to undergo apoptosis may provide novel opportunities for cancer drug development. Thus, apoptosis pathways may be exploited for cancer treatment by directly triggering cell death in tumor cells, e.g. via ligation of death receptors, or by enhancing the efficacy of conventional cancer therapies, e.g. by blockade of anti-apoptotic programs. In this review we will focus on the potential exploitation of the death receptor pathway, in particular TRAIL, for cancer therapy. Also, we will discuss signal transduction therapy targeting Inhibitor of Apoptosis Proteins (IAPs).