TY - JOUR
T1 - Gene replacement strategies for treating non-small cell lung cancer
AU - Roth, Jack A.
AU - Grammer, Susan F.
AU - Swisher, Stephen G.
AU - Nemunaitis, John
AU - Merritt, James
AU - Meyn, Raymond E.
N1 - Funding Information:
From the Departments of Thoracic and Cardiovascular Surgery, and Experimental Radiation Oncology, The University of Texas M.D. Anderwn Cancer Center,"B iotechwrite:Biomedical and Science Communications," and Introgen Therapeutics, Inc, Ho~ton, TX," and US Ontology, Bqffor University Medical Center. Dallas, TX. Supported bY grantsf rom the National CancerI nstitute and the National Institutes of Health (POI CA78778-OIA1) (\].A.R.); bY a grant for a Specialized Program of Research Excellence (SPORE) in Lung Cancer (P50-CA 70907); bY gij2s to the 1)ivi~ion of Surgery and Anesthesiology.from Tenneco and Exxon for the Core Laboratory Facility; by the University of Texas M.D. Anderson Cancer Center Support Core Grant (CA16672); and by a sponsoredr esearch agreement with Introgen Therapeutics, Inc. Address reprint requests to Jack A. Roth, MD, Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. Copyright 9 2000 by W.B. Saunders Company 1053-4296/00/1004-0010510.00/0 do# l O.1 053/srao.2000.912 7
PY - 2000
Y1 - 2000
N2 - Fewer than 15% of the 170,000 patients who develop lung cancer each year will survive their disease, which shows the need for novel, more specific, and less toxic therapeutic strategies. Recent advances in molecular biology have made it possible to ascertain which genetic alterations contribute to the etiology of cancer. For example, the tumor-suppressor gene, p53, responsible for directing repair of damaged DNA or committing a cell to apoptosis, is mutated or otherwise altered in more than 50% of cancers, including 40% to 70% of non-small cell lung cancers. Many p53-deficient tumors have proven remarkably resistant to radiotherapy and chemotherapy. The preclinical and clinical studies of gene therapy reviewed in this article show (1) successful transfer and expression of a potentially therapeutic p53 gene construct in tumor cells, (2) observation of antitumor effects in vitro and in vivo, and (3) most critically, a lack of significant toxicity. The results of these studies indicate that gene replacement therapy is a feasible alternative therapy for cancer. In addition, these studies show that transfer of the p53 gene can induce radiation sensitization in previously radiation-resistant tumors, leading to the possibility of new therapeutic protocols combining gene replacement with radiation therapy. Copyright (C) 2000 by W.B. Saunders Company.
AB - Fewer than 15% of the 170,000 patients who develop lung cancer each year will survive their disease, which shows the need for novel, more specific, and less toxic therapeutic strategies. Recent advances in molecular biology have made it possible to ascertain which genetic alterations contribute to the etiology of cancer. For example, the tumor-suppressor gene, p53, responsible for directing repair of damaged DNA or committing a cell to apoptosis, is mutated or otherwise altered in more than 50% of cancers, including 40% to 70% of non-small cell lung cancers. Many p53-deficient tumors have proven remarkably resistant to radiotherapy and chemotherapy. The preclinical and clinical studies of gene therapy reviewed in this article show (1) successful transfer and expression of a potentially therapeutic p53 gene construct in tumor cells, (2) observation of antitumor effects in vitro and in vivo, and (3) most critically, a lack of significant toxicity. The results of these studies indicate that gene replacement therapy is a feasible alternative therapy for cancer. In addition, these studies show that transfer of the p53 gene can induce radiation sensitization in previously radiation-resistant tumors, leading to the possibility of new therapeutic protocols combining gene replacement with radiation therapy. Copyright (C) 2000 by W.B. Saunders Company.
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U2 - 10.1053/srao.2000.9127
DO - 10.1053/srao.2000.9127
M3 - Article
C2 - 11040334
AN - SCOPUS:0033789477
SN - 1053-4296
VL - 10
SP - 333
EP - 342
JO - Seminars in radiation oncology
JF - Seminars in radiation oncology
IS - 4
ER -