Chemoprotection by transfer of resistance genes.
Dose-limiting toxicity of chemotherapeutic agents, i.e., myelosuppression, can limit their effectiveness. The transfer and expression of drug-resistance genes might decrease the risks associated with acute hematopoietic toxicity. Protection of hematopoietic stem/progenitor cells by transfer of drug-resistance genes provides the possibility of intensification or escalation of antitumor drug doses and consequently an improved therapeutic index. This chapter reviews drug-resistance gene transfer strategies for either myeloprotection or therapeutic gene selection. Selecting candidate drug-resistance gene(s), gene transfer methodology, evaluating the safety and the efficiency of the treatment strategy, relevant in vivo models, and oncoretroviral transduction of human hematopoietic stem/progenitor cells under clinically applicable conditions are described.
Budak-Alpdogan
Tulin
T
Department of Medicine, The Cancer Institute of New Jersey, Robert Wood Johson Medical School, University of Medicine & Dentistry of New Jersey, New Brunswick, NJ, USA.
Bertino
Joseph R
JR
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D003114:Colony-Forming Units Assay; D019610:Cytoprotection / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D016133:Polymerase Chain Reaction; D014161:Transduction, Genetic
D018952:Antigens, CD34