Trabectedin (Yondelis®) as a Therapeutic Option in Gynecological Cancers: A Focus on its Mechanisms of Action, Clinical Activity and Genomic Predictors of Drug Response

Curr Drug Targets. 2020;21(10):996-1007. doi: 10.2174/1389450121666200128161733.

Abstract

The use of predictive biomarkers provides potential individualized cancer therapeutic options to prevent therapy failure as well as serious toxicities. Several recent studies showed that predictive and prognostic biomarkers are a notable personalized strategy to improve patients' care in several cancers. Trabectedin (Yondelis®) is a cytotoxic agent, derived from a marine organism, harbouring a significant antitumor activity against several cancers such as soft tissue sarcoma, ovarian, and breast cancers. Recently and with the advent of molecular genetic testing, BRCA mutational status was found as an important predictor of response to this anticancer drug, especially in gynecological cancers. The aim of this updated review is to discuss the mechanisms of action of trabectedin against the wellknown cancer hallmarks described until today. The current advances were also examined related to genomic biomarkers that can be used in the future to predict the efficacy of this potent anticancer natural molecule in various gynecological cancers.

Keywords: Trabectedin; gynecological cancers; ovarian cancer; predictive biomarkers; uterine leiomyosarcoma.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Biomarkers, Pharmacological
  • Breast Neoplasms / drug therapy*
  • Female
  • Genital Neoplasms, Female / drug therapy*
  • Genomics
  • Humans
  • Trabectedin / pharmacology*
  • Trabectedin / therapeutic use*

Substances

  • Antineoplastic Agents, Alkylating
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • Biomarkers, Pharmacological
  • Trabectedin