title: Oxaliplatin in the era of personalized medicine: from mechanistic studies to clinical efficacy.
abstract: Oxaliplatin is a third-generation platinum compound approved for clinical use relatively recently as compared to other drugs of the same class. Its main cellular target is DNA, where similarly to cisplatin and carboplatin it forms cross-links. However, due to a unique indication for colorectal cancer, synergistic interaction with fluoropyrimidines and peculiar toxicity profile, oxaliplatin is different from those compounds. Multiple lines of evidence indicate differences in transport and metabolism, consequences of DNA platination, as well as DNA repair and transduction of DNA damage. Here, we explore the preclinical features that may explain the unique properties of oxaliplatin in the clinics. Among them, the capability to accumulate in tumor cells via organic cation transporters, to kill KRAS mutant cells and to activate immunogenic cell death appears helpful to explain in part its clinical behavior. The continuous investigation of the molecular pharmacology of oxaliplatin is expected to provide clues to the definitions of predictors of drug activity and toxicity to translate to the clinical setting.
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133, Milan, Italy. paola.perego@istitutotumori.mi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Perego
authors.affiliation: INSERM U916, Institut Bergonié, University of Bordeaux, 229 Cours de l'Argonne, 33000, Bordeaux, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000494:pharmacology*; D000077150:Oxaliplatin; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: DNA repair; Drug accumulation; Oxaliplatin; Personalized medicine; Survival pathways