Tumor-Related Molecular Mechanisms of Oxaliplatin Resistance

Mol Cancer Ther. 2015 Aug;14(8):1767-76. doi: 10.1158/1535-7163.MCT-14-0636. Epub 2015 Jul 16.

Abstract

Oxaliplatin was the first platinum drug with proven activity against colorectal tumors, becoming a standard in the management of this malignancy. It is also considered for the treatment of pancreatic and gastric cancers. However, a major reason for treatment failure still is the existence of tumor intrinsic or acquired resistance. Consequently, it is important to understand the molecular mechanisms underlying the appearance of this phenomenon to find ways of circumventing it and to improve and optimize treatments. This review will be focused on recent discoveries about oxaliplatin tumor-related resistance mechanisms, including alterations in transport, detoxification, DNA damage response and repair, cell death (apoptotic and nonapoptotic), and epigenetic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Biological Transport
  • Cell Death / drug effects
  • Cell Death / genetics
  • DNA Adducts / metabolism
  • DNA Repair
  • Drug Resistance, Neoplasm*
  • Epigenesis, Genetic
  • Humans
  • Inactivation, Metabolic
  • Lymphocyte Activation / immunology
  • NF-kappa B / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Organoplatinum Compounds / pharmacology*
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • NF-kappa B
  • Organoplatinum Compounds
  • Oxaliplatin