Cisplatin resistance and opportunities for precision medicine

Pharmacol Res. 2016 Apr:106:27-36. doi: 10.1016/j.phrs.2016.01.001. Epub 2016 Jan 22.

Abstract

Cisplatin is one of the most commonly used chemotherapy drugs, treating a wide range of cancer types. Unfortunately, many cancers initially respond to platinum treatment but when the tumor returns, drug resistance frequently occurs. Resistance to cisplatin is attributed to three molecular mechanisms: increased DNA repair, altered cellular accumulation, and increased drug inactivation. The use of precision medicine to make informed decisions on a patient's cisplatin resistance status and predicting the tumor response would allow the clinician to tailor the chemotherapy program based on the biology of the disease. In this review, key biomarkers of each molecular mechanism will be discussed along with the current clinical research. Additionally, known polymorphisms for each biomarker will be discussed in relation to their influence on cisplatin resistance.

Keywords: ABC transporters; Cisplatin resistance; Copper transporters; ERCC1; Glutathione; Nucleotide excision repair.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Cisplatin / adverse effects*
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Neoplasms / drug therapy*
  • Precision Medicine / methods*

Substances

  • Antineoplastic Agents
  • Cisplatin