TRAIL and chemotherapeutic drugs in cancer therapy.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a recently identified member of the TNF ligand family that selectively induces apoptosis in tumor cells in vitro and in vivo but not in most normal cells. Chemotherapeutic drugs induce apoptosis and the upregulation of death receptors or activation of intracellular signaling pathways of TRAIL. Numerous chemotherapeutic drugs have been shown to sensitize tumor cells to TRAIL-mediated apoptosis. Studies from our laboratory have also shown that TRAIL-resistant renal cell carcinoma, prostate gland cancer, and bladder cancer cells are sensitized by subtoxic concentrations of chemotherapeutic drugs including doxorubicin, epirubicin, pirarubicin, and cisplatin. TRAIL, particularly in combination with chemotherapeutic agents, is thus potentially promising in the treatment of cancer. This review addresses the putative role of TRAIL in cancer treatment and discusses the molecular basis of the synergistic effect of TRAIL and chemotherapeutic drugs.