Gene therapy for liver cancer: clinical experience and future prospects.
In contrast to the large quantity of preclinical evidence for efficacy, few gene therapy agents have reached clinical development for the treatment of primary and secondary liver cancer. This review discusses the published clinical trials that have explored the feasibility, safety and efficacy of gene therapy strategies for the treatment of liver cancer. Strategies include restoration of tumor suppressor genes, genetic prodrug-activating therapy, genetic immunotherapy and oncolytic virotherapy. In these trials, transgene expression of varying degrees has been detected. Globally, gene therapy has proven to be safe, with none of the agents tested reaching the MTD. Although none of the phase II trials provided significant response rates, objective remissions have occasionally been observed and proof-of-concept for the ability of gene therapy to produce significant tumor cell killing has been determined. Insufficient delivery following intravascular administration and short-lived transgene expression are likely to be the cause of this limited antitumor efficacy. The development of new gene therapy vectors with improved characteristics will increase the probability of success of gene therapy for the treatment of liver cancer.
Sangro
Bruno
B
Clinica Universitaria de Navarra, Liver Unit, Avenida Pio XII 36, 31008 Pamplona, Spain. bsangro@unav.es
Prieto
Jesus
J
D006528:Carcinoma, Hepatocellular / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods