Oxaliplatin in the era of personalized medicine: From mechanistic studies to clinical efficacy Cytotoxic Reviews Godefridus J. Peters and Eric Raymond

Paola Perego, Jacques Robert

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5-18
Number of pages14
JournalCancer Chemotherapy and Pharmacology
Volume77
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

Keywords

  • DNA repair
  • Drug accumulation
  • Oxaliplatin
  • Personalized medicine
  • Survival pathways

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

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