A review of trabectedin (ET-743): a unique mechanism of action.

Abstract:

:Trabectedin (ET-743) is a marine alkaloid isolated from the Caribbean tunicate Ecteinascidia turbinata, with a chemical structure characterized by three fused tetrahydroisoquinoline rings. Two of these rings (subunits A and B) provide the framework for covalent interaction with the minor groove of the DNA double helix, whereas the third ring (subunit C) protrudes from the DNA duplex, apparently allowing interactions with adjacent nuclear proteins. The compound's chemical interactions trigger a cascade of events that interfere with several transcription factors, DNA binding proteins, and DNA repair pathways, likely to be different from other DNA-interacting agents. Trabectedin also causes modulation of the production of cytokines and chemokines by tumor and normal cells, suggesting that the antitumor activity could also be ascribed to changes in the tumor microenvironment. The promising data on the combination of trabectedin with other anticancer agents, observed in preclinical systems, have prompted several clinical studies that are currently ongoing. One of these combinations (trabectedin-pegylated liposomal doxorubicin) was recently authorized by the European Commission for the treatment of patients with relapsed platinum-sensitive ovarian cancer.

journal_name

Mol Cancer Ther

authors

D'Incalci M,Galmarini CM

doi

10.1158/1535-7163.MCT-10-0263

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

2157-63

issue

8

eissn

1535-7163

issn

1538-8514

pii

1535-7163.MCT-10-0263

journal_volume

9

pub_type

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