[Targeted drugs in radiation therapy].
New drugs aiming at the development of targeted therapies have been assayed in combination with ionizing radiation over the past few years. The rationale of this concept comes from the fact that the cytotoxic potential of targeted drugs is limited, thus requiring concomitant association with a cytotoxic agent for the eradication of tumor cells. Conversely a low level of cumulative toxicity is expected from targeted drugs. Most targeted drugs act through inhibition of post-translational modifications of proteins, such as dimerization of growth factor receptors, prenylation reactions, or phosphorylation of tyrosine or serine-threonine residues. Many systems involving the proteasome, neoangiogenesis promoters, TGF-beta, cyclooxygenase or the transcription factor NF-kappaB, are currently under investigation in hopes they will allow a control of cell proliferation, apoptosis, cell cycle progression, tumor angiogenesis and inflammation. A few drugs have demonstrated an antitumor potential in particular phenotypes. In most instances, however, radiation-drug interactions proved to be strictly additive in terms of cell growth inhibition or induced cell death. Strong potentiation of the response to radiotherapy is expected to require interaction with DNA repair mechanisms.
Favaudon
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V
U612 Inserm et institut Curie-Recherche, bâtiments 110-112, centre universitaire, 91405 Orsay, France. vincent.favaudon@curie.u-psud.fr
Hennequin
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D000068818:Cetuximab; D017321:Clinical Trials, Phase I as Topic; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D006801:Humans; D000068877:Imatinib Mesylate; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D000068877:Imatinib Mesylate; D066246:ErbB Receptors; D000068878:Trastuzumab; D000068818:Cetuximab; D000077156:Gefitinib