title: [Pharmacological targeting of Mdm2: rationale and perspectives for radiosensitization].
abstract: The central role of p53 after exposure to ionizing radiation has been widely demonstrated. Mdm2, the main cellular regulator of p53, is a promising target for radiosensitizing purposes. In this article, we review the most recent data on the pharmacological targeting of Mdm2, with focus on strategies of radiosensitization. Antitumor activity of Mdm2 inhibitors has been related with activation of p53-dependant apoptosis, action on DNA repair systems, and antiangiogenic activity. Preliminary data suggested a synergic interaction between Mdm2 inhibitors and ionizing radiations. However, no clinical data has been published yet on the pharmacological targeting of Mdm2. Given their new mechanisms of action, these new molecules should be subject to careful clinical assessment. Although promising, these strategies expose to unexpected toxicities.
authors.affiliation: Upres EA 27-10, laboratoire de radiobiologie, institut de cancérologie Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Chargari
authors.forename: C
authors.initials: C
authors.lastname: Leteur
authors.forename: C
authors.initials: C
authors.lastname: Ferté
authors.forename: M
authors.initials: M
authors.lastname: Deberne
authors.forename: B
authors.initials: B
authors.lastname: Lahon
authors.forename: C
authors.initials: C
authors.lastname: Rivera
authors.forename: J
authors.initials: J
authors.lastname: Bourhis
authors.forename: E
authors.initials: E
authors.lastname: Deutsch
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy; D051736:Proto-Oncogene Proteins c-mdm2 / Q000187:drug effects* / Q000502:physiology; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D011838:Radiation-Sensitizing Agents; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2