apeutics ew eview of Trabectedin ( ET - 743 ) : A Unique Ther

ownload ectedin (ET-743) is a marine alkaloid isolated from the Caribbean tunicate Ecteinascidia turbinata, with ical structure characterized by three fused tetrahydroisoquinoline rings. Two of these rings (subunits B) provide the framework for covalent interaction with the minor groove of the DNA double helix, as the third ring (subunit C) protrudes from the DNA duplex, apparently allowing interactions with nt nuclear proteins. The compound's chemical interactions trigger a cascade of events that interfere everal transcription factors, DNA binding proteins, and DNA repair pathways, likely to be different ther DNA-interacting agents. Trabectedin also causes modulation of the production of cytokines and kines by tumor and normal cells, suggesting that the antitumor activity could also be ascribed to es in the tumor microenvironment. The promising data on the combination of trabectedin with other ncer agents, observed in preclinical systems, have prompted several clinical studies that are currently g. One of these combinations (trabectedin-pegylated liposomal doxorubicin) was recently authorized ongoin by the European Commission for the treatment of patients with relapsed platinum-sensitive ovarian cancer. Mol Cancer Ther; 9(8); 2157–63. ©2010 AACR.