title: Wide-spectrum characterization of trabectedin: biology, clinical activity and future perspectives.
abstract: Ecteinascidin-743 (trabectedin, Yondelis((R)); 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.
authors.affiliation: University Campus Bio-Medico, Medical Oncology, Via Alvaro del Portillo 200, 00128 Rome, Italy. b.vincenzi@unicampus.it
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Napolitano
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frezza
authors.forename: Gaia
authors.initials: G
authors.lastname: Schiavon
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D002986:Clinical Trials as Topic; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004149:Dioxoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000077606:Trabectedin; D014561:Urochordata / Q000737:chemistry
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018736:DNA Adducts; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin