title: Resistance acquisition to MDM2 inhibitors.
abstract: Various experimental strategies aim to (re)activate p53 signalling in cancer cells. The most advanced clinically are small-molecule inhibitors of the autoregulatory interaction between p53 and MDM2 (murine double minute 2). Different MDM2 inhibitors are currently under investigation in clinical trials. As for other targeted anti-cancer therapy approaches, relatively rapid resistance acquisition may limit the clinical efficacy of MDM2 inhibitors. In particular, MDM2 inhibitors were shown to induce p53 mutations in experimental systems. In the present article, we summarize what is known about MDM2 inhibitors as anti-cancer drugs with a focus on the acquisition of resistance to these compounds.
authors.affiliation: *Institut für Medizinische Virologie, Klinikum der Goethe-Universität, Paul-Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany.
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
authors.forename: Daniel
authors.initials: D
authors.lastname: Speidel
authors.affiliation: §School of Chemistry, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K.
authors.forename: Ian
authors.initials: I
authors.lastname: Hardcastle
authors.affiliation: ∥Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury CT5 3RL, U.K.
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2