Gene replacement strategies for lung cancer.
Considerable evidence has accumulated that cancer has a genetic origin based on the development of somatic mutations in families of genes responsible for critical functions of cellular DNA repair, growth control, and division. Restoration of the function of a single pivotal gene product appears sufficient to mediate antitumor effects that are potentially clinically significant. For example, restoration of wild-type p53 function in the cancer cell by gene transfer is sufficient to cause either cell-cycle arrest or apoptosis. This effect is not restricted to p53 but has been observed for oncogenes and other tumor suppressor genes as well. Genes can be delivered with sufficient efficiency by direct intratumoral injection to mediate tumor regression as shown in preclinical studies and phase I clinical trials in non-small cell lung cancer. Although clinical trials of gene replacement are in the earliest stages, this treatment offers a unique mechanism of action with a potentially high therapeutic index.
Roth
J A
JA
Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*