Adenovirus-mediated p53 gene therapy: overview of preclinical studies and potential clinical applications.
Disruption of p53 function through mutation, or other means, occurs very frequently in human cancer and is associated with an unfavorable prognosis in various cancers. Evidence from in vitro and in vivo transduction experiments have demonstrated that adenoviral-mediated expression of wild-type p53 suppresses the transformed phenotype of many cell types and potentiates the cytotoxicity of both chemotherapeutic agents and radiation therapy. Recently several phase I studies have evaluated the safety, biological effect and different routes of administration of adenoviral-mediated p53 gene therapy in various tumor types. These studies indicate that adenovirus-mediated p53 gene therapy and introduction of wild-type p53 into tumor cells represents a potentially valuable tool for the therapy of many types of human cancers. This review presents an overview of the most recent advances in the preclinical and clinical evaluation of adenoviral p53 gene therapy as well as the challenges that lay ahead forfuture clinical studies.
Horowitz
J
J
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. JO.ANN.HOROWITZ@spcorp.com
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000556:secondary / Q000628:therapy; D006528:Carcinoma, Hepatocellular / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy; D002945:Cisplatin / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006258:Head and Neck Neoplasms / Q000628:therapy; D006801:Humans; D007267:Injections; D007376:Interleukin-2 / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000628:therapy; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D017239:Paclitaxel / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016879:Salvage Therapy; D015398:Signal Transduction; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel; D002945:Cisplatin