Cancer gene therapy: Connecting basic research with clinical inquiry

Molecular genetics has spawned an impressive outpouring of insights into the biology of neoplastic transformation and the host-tumor relationship. This deeper understanding of cancer pathogenesis presents a rich opportunity ta develop novel therapeutic agents with improved selectivity for cancer cells. One promising approach involves gene therapy, which is the introduction of genetic material into a patient's tissues with the intent to achieve therapeutic benefit. A number of gene transfer systems have been designed that enable the generic modification of relevant target cells, albeit with varying strengths and limitations. Several strategies to exploit gene transfer as a tool to target specific molecular defects intrinsic to cancer cells, enhance tumor chemosensitivity, and augment tumor immunogenicity are under intensive investigation. A number of these approaches have entered initial clinical testing and already provide intriguing new information about the biology of cancer in patients. In this review, I will highlight the critical issues and controversies that underscore preclinical experiments in cancer gene therapy, discuss some of the preliminary findings from the first wave of clinical trials, and speculate about the prospects that cancer gene therapy will change the way that cancer medicine is practiced. (C) 1998 by American Society of Clinical Oncology.