Format

Send to

Choose Destination
See comment in PubMed Commons below
Future Oncol. 2013 Dec;9(12 Suppl):5-10. doi: 10.2217/fon.13.207.

Trabectedin mechanism of action: what's new?

Author information

1
Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. maurizio.dincalci@marionegri.it.

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.

PMID:
24195524
DOI:
10.2217/fon.13.207
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Support Center