Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its therapeutic potential in breast and gynecologic cancers

OBJECTIVE: The relationship between the apoptotic pathway and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising area of scientific interest for cancer researchers. TRAIL-receptor-activating agents have demonstrated favorable in vitro and in vivo activity for the treatment of several malignancies including breast and gynecologic cancers. METHODS: This article reviews the available peer-reviewed literature and our own institution's experience with specific TRAIL-receptor-activating agents. Emphasis was placed on the apoptotic/TRAIL mechanism, preclinical evaluation, and phase I studies in various malignancies. RESULTS: Preclinical and early phase I studies indicate that these novel agents are safe with enhanced target specificity for malignancy. When these targeted agents are combined with conventional chemotherapy drugs or radiation therapy, they appear to increase cell death over single-agent modalities. CONCLUSIONS: TRAIL-receptor-activating agents represent an exciting new class of targeted therapies that hold promise to improve the treatment of women with breast and gynecologic malignancies.