Oxygen delivery: implications for the biology and therapy of solid tumors.
Solid malignancies develop areas of hypoxia during the earliest phase of their development, while they are still microscopic in size and before they have initiated angiogenesis. The physiologic effects of hypoxia and the associated microenvironmental inadequacies increase mutation rates, select for cells deficient in normal pathways of programmed cell death, and contribute to the development of an increasingly invasive, metastatic phenotype. Hypoxic tumor cells are also resistant to radiation and to many antineoplastic drugs, and can limit the curability of solid tumors by radiotherapy and chemotherapy. This article reviews several approaches to improving tumor oxygenation and discusses the results of laboratory and clinical studies examining their efficacy in improving the outcome of radiation therapy. Past clinical trials, using nonoptimal agents and regimens to circumvent the protective effects of hypoxia, improved local control rates by approximately 10%. Greater improvements should be possible when the new agents now undergoing laboratory testing are used in optimally designed clinical regimens.
Rockwell
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Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA. sara.rockwell@yale.edu
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004357:Drug Synergism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D010100:Oxygen / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D010100:Oxygen