Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for treatment of prostate cancer: first results and review of the literature

We present the involvement and association of TNF-related apoptosis-inducin g ligand (TRAIL) with apoptosis. Its potential application as a therapeutic agent in urologic oncology is discussed. We have examined the sensitivity of prostate carcinoma cell lines DU145, PC3 and LNCaP to TRAIL-induced apop tosis and the expression of TRAIL receptors. Furthermore we looked into the sensitization of those prostate carcinoma cell lines to TRAIL-mediated apo ptosis by low toxic levels of actinomycin-D. Furthermore, we review and dis cuss the pertinent literature on the molecular biology of TRAIL, its recept ors and future potential for therapy in urologic oncology. Recent discovery and characterization of TRAIL has led to further broadenin g and insights into the apoptotic process. Based on preceding in-vitro stud ies, the first in-vivo study using TRAIL has been conducted and published i n 1999. Systemic application of TRAIL in severe combined immune deficient ( SCID) mice resulted in tumor regression of subcutaneous implanted mammary a nd colon cancer and several groups are looking into TRAIL sensitivity of pr ostate cancer and renal cancer cellines. Our in-vitro data revealed a signi ficant increase of apoptotic cell death rate following the combined applica tion of TRAIL with actinomycin-D. Our results suggest that the combination of TRAIL and ActD may be a therape utic option in the treatment of drug/hormone refractory prostate carcinoma. In the future TRAIL may be used in combination therapy with other immunoth erapies or gene therapies providing a synergistic effect or enhancing the e fficacy of chemotherapeutic or radiotherapeutic regimens.