p53 gene therapy for human cancer: Presence and future of clinical trials

Recent advances in molecular biology have fostered remarkable insights into the molecular basis of neoplasms. Considerable evidence has accumulated that some of the mechanisms of human cancer development are the overexpression of dominant oncogenes, expression of mutant oncogenes, or specific chromosomal deletions or mutations that induce inactivation of tumor - suppressor activity. This understanding of cancer pathogenesis suggests that restoration of the function of critical gene products could halt or reverse these mechanisms, and thus have a therapeutic effect on cancer. The tumor suppressor p53 gene has been implicated in many inherited and sporadic forms of malignancies in humans. A number of preclinical experiments have demonstrated that restoration of the wild-type p53 function in the cancer cell by gene transfer is sufficient to cause antitumor effects such as cell- cycle arrest and induction of apoptosis. This approach has entered initial clinical testing and provided intriguing information about the intratumoral administration of an adenovirus vector expressing the wild-type p53 gene in non-small cell lung cancer patients. This article reviews recent highlights in the rapidly evolving field of p53 gene therapy for human cancer.