Molecular approaches to potentiate cisplatin responsiveness in carcinoma therapeutics

Expert Rev Anticancer Ther. 2017 Sep;17(9):815-825. doi: 10.1080/14737140.2017.1356231. Epub 2017 Jul 20.

Abstract

Cisplatin has been considered as the crucial regimen of widely prescribed chemotherapy treatment for cancer. The advancing treatment of cancers has reached the border line, where tumors show resistance to cisplatin and may thwart its use. Other than issues of drug resistance, cisplatin has been reported to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there is a compelling need to untangle the problems associated with cisplatin treatment in carcinoma. Areas covered: In this review, we summarize the current status of combinatorial options to bring about better pre-clinical and clinical cisplatin drug responses in carcinoma. We begin with problems associated with cisplatin drugs and current avenues such as depicting molecular modulation of enhanced influx and reduced efflux. We also discuss the scope of the DNA damage response landscape and contribution of regulatory small RNAs towards potentiation of cisplatin responses. Expert commentary: The extensive use of cisplatin and incessant high drug dose have prompted the scientific community to limit the burden of cisplatin without compromising therapeutic success. Currently, there are reports on the potential use of other non-toxic small molecule inhibitors, interference RNAs and peptide mimetics to get rid of cellular adversities responsible for cisplatin resistance and high dose effects.

Keywords: Chemotherapy; DNA repair; carcinoma; cisplatin; drug resistance; epigenetic; microRNA.

Publication types

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

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • DNA Damage
  • Drug Resistance, Neoplasm
  • Ear Diseases / chemically induced
  • Humans
  • Kidney Diseases / chemically induced
  • RNA, Small Interfering / administration & dosage

Substances

  • Antineoplastic Agents
  • RNA, Small Interfering
  • Cisplatin