Wide-spectrum characterization of trabectedin: Biology, clinical activity and future perspectives

Bruno Vincenzi, Andrea Napolitano, Anna Maria Frezza, Gaia Schiavon, Daniele Santini, Giuseppe Tonini

Research output: Contribution to journalArticle

Abstract

Ecteinascidin-743 (trabectedin, Yondelis®; PharmaMar, Madrid, Spain), a 25-year-old antineoplastic alkylating agent, has recently shown unexpected and interesting mechanisms of action. Trabectedin causes perturbation in the transcription of inducible genes (e.g., the multidrug resistance gene MDR1) and interaction with DNA repair mechanisms (e.g., the nucleotide excision repair pathway) owing to drug-related DNA double strand breaks and adduct formation. Trabectedin was the first antineoplastic agent from a marine source (namely, the Caribbean tunicate Ecteinascidia turbinata) to receive marketing authorization. This article summarizes the mechanisms of action, the complex metabolism, the main toxicities, the preclinical and clinical evidences of its antineoplastic effects in different types of cancer and, finally, the future perspectives of this promising drug.

Original languageEnglish
Pages (from-to)865-878
Number of pages14
JournalPharmacogenomics
Volume11
Issue number6
DOIs
Publication statusPublished - 2010

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Keywords

  • Adducts
  • Cancer
  • Double strand breaks
  • ET-743
  • MDR1
  • NER
  • Ovarian
  • Sarcomas
  • Therapy
  • Trabectedin

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine
  • Medicine(all)

Cite this

Vincenzi, B., Napolitano, A., Frezza, A. M., Schiavon, G., Santini, D., & Tonini, G. (2010). Wide-spectrum characterization of trabectedin: Biology, clinical activity and future perspectives. Pharmacogenomics, 11(6), 865-878. https://doi.org/10.2217/pgs.10.69