TRAIL receptor-targeted therapy.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines. Based on its ability to induce apoptosis selectively in a wide variety of cancer cell lines and human tumor xenografts, TRAIL has been in drug development as a potential biological agent for cancer therapy. A variety of chemotherapy agents have been shown to enhance the cytotoxic effects of TRAIL. The potential benefits of TRAIL as an anticancer therapy have been further indicated by its ability to enhance the efficacy of radiotherapy. Preclinical studies have shown the potential use of agonistic monoclonal antibodies that selectively bind TRAIL death receptors for cancer therapy. This review provides an overview of TRAIL receptor-mediated apoptosis of tumor cells, with TRAIL or agonistic monoclonal antibodies only or with chemotherapy drugs. Treatment of tumor xenografts with these ligands, alone or in combination with chemotherapy or radiation, are discussed along with preliminary information about early clinical trials. Additional clinical trials with TRAIL receptor ligands in combination treatment regimens are required to determine their potential for targeted therapy of cancer.