title: Therapeutic targets in radiotherapy.
abstract: BACKGROUND
  Enormous progress has been made in the past 5 years in our understanding of the gene products governing the response of mammalian cells to ionizing radiation. Many of these are potential targets for enhancing the effectiveness of radiotherapy. However, a major barrier to such efforts is the requirement for a preferential effect on tumor vs. normal cells. Such a requirement can only come about by exploiting a known difference between tumor and normal cells.
  
  
  METHODS
  This review highlights three differences between tumor and normal cells that are being exploited with fractionated radiotherapy.
  
  
  RESULTS
  The three strategies to enhance preferentially tumor response to radiotherapy are inhibition of ras activity using farnesyltransferase inhibitors (FTIs), inhibition of epidermal growth factor receptors (EGFRs), and the use of drugs that preferentially kill hypoxic cells. Each of these strategies exploits a known difference between at least some tumors and their surrounding normal tissues, and each has shown encouraging results when combined with fractionated radiation in preclinical studies.
  
  
  CONCLUSIONS
  For each of the three strategies to enhance preferentially the sensitivity of cancers, the preclinical and early clinical data are promising for their successful application in radiotherapy.
authors.affiliation: Division of Radiation Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305-5152, USA. mbrown@leland.stanford.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Brown
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051231:Farnesyltranstransferase; D011905:Genes, ras / Q000187:drug effects / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D015398:Signal Transduction; D000077704:Tirapazamine; D014227:Triazines / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C096856:FTI 277; D011838:Radiation-Sensitizing Agents; D014227:Triazines; D000077704:Tirapazamine; D008715:Methionine; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D066246:ErbB Receptors