Trabectedin is an antineoplastic from the alkylating agent drug class. It is derived from a marine-derived antitumor molecule discovered in the Caribbean tunicate Ecteinascidia turbinata. This drug is indicated in the treatment of advanced soft tissue sarcoma (liposarcoma or leiomyosarcoma) in Europe, Russia, and South Korea. It is also approved as an orphan drug by the FDA for the treatment of soft tissue sarcomas and ovarian cancer. Trabectedin binds covalently to the DNA minor groove. This molecule binds and alkylates guanine bases to the N2 position with its two rings in its structure, causing the equivalent of a functional interstrand crosslink. The third ring protrudes from the DNA strand which lets it interact with nearby nuclear proteins. It affects various transcription factors involved in cell proliferation via the transcription-coupled nucleotide excision repair system (NER). With this mechanism of action, trabectedin blocks the cell cycle at the G2 phase, resulting in the apoptosis of the cancerous cell, This drug is administered as an intravenous injection.

Trabectedin Pathway References