Trabectedin mechanism of action: What's new?

Research output: Contribution to journalArticle

Abstract

Trabectedin is a tetrahydroisoquinoline molecule that binds to the N2 of guanine in the minor groove, causing DNA damage and affecting transcription regulation in a promoter- and gene-specific manner. The antitumor activity of trabectedin appears to be not only related to its direct effects on cancer cells, but also on the tumor microenvironment. In cancer cells, the drug induces cell cycle arrest and cell death that is not dependent on p53 status, and it is increased dramatically in cells deficient in homologous recombination (e.g., cells with mutations of BRCA1/2). Trabectedin also has potent immunomodulatory effects, being selectively cytotoxic against monocytes and tumor-associated macrophages. In addition, it inhibits production of proinflammatory and angiogenic mediators, which induces changes in the tumor microenvironment and contributes to its antitumor activity. The opportunity to combine direct cytotoxic activity with a capacity to favorably modify the tumor microenvironment, using either single-agent or combination therapy, is an especially appealing therapeutic option for a diverse range of cancers.

Original languageEnglish
Pages (from-to)5-10
Number of pages6
JournalFuture Oncology
Volume9
Issue number12 SUPPL.
DOIs
Publication statusPublished - Dec 2013

Keywords

  • antitumor activity
  • mechanism of action
  • trabectedin
  • tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Trabectedin mechanism of action: What's new?'. Together they form a unique fingerprint.

  • Cite this