trabectedin
Meaning of trabectedin: A chemotherapy drug first found in a Caribbean sea squirt, which jams DNA repair rather than simply breaking the strands.
Definition of trabectedin
Trabectedin is a chemotherapy drug used to treat certain soft tissue sarcomas and ovarian cancer. It was first isolated from a marine animal, the sea squirt Ecteinascidia turbinata, and is now produced by chemical synthesis. It binds within the groove of the DNA double helix, bends the strand, and interferes with both the reading of genes and the machinery that repairs damaged DNA.
How does it act on DNA?
Most chemotherapy either breaks DNA or blocks its copying. Trabectedin does something less usual. It slots into the minor groove, the narrower of the two spiral channels running along the double helix, and attaches to a specific base. The helix bends toward the wider groove. That distortion blocks the machinery that reads genes into messages and traps repair proteins at the site, so the repair attempt itself generates a break the cell cannot resolve. Cells that rely most heavily on that particular repair route are therefore the most vulnerable, which is one explanation for why the drug works in tumor types where several other agents do not. Trabectedin also acts on the immune cells a tumor gathers around itself, reducing the supporting cells that help it grow, an effect separate from anything it does to DNA.
What is it used for?
| Disease | Notes |
|---|---|
| Liposarcoma | A sarcoma arising in fat tissue |
| Leiomyosarcoma | A sarcoma arising in smooth muscle |
| Ovarian cancer | Used in combination, after earlier treatment |
Sarcomas are uncommon cancer types arising in connective tissue rather than in the lining of an organ, and the treatment options for them are comparatively few, which is part of why this drug matters despite its narrow indications.
Why does its origin matter?
Harvesting sea squirts on the scale needed for a medicine was never realistic, and total chemical synthesis solved that. The compound also carries the older research name ecteinascidin 743, and both names appear in the literature. It is given by infusion through a central line, because leakage into surrounding tissue causes severe local damage. Liver enzyme rises and muscle breakdown are recognized effects and are watched during treatment, and the drug is broken down by the liver, so it interacts with medicines and foods that affect those enzymes.
Also known as
Used in a sentence
Trabectedin was selected following progression on first-line treatment for leiomyosarcoma.
Good to know
Trabectedin has approved uses in soft tissue sarcoma and ovarian cancer rather than being purely investigational, and leakage from the vein causes severe local tissue injury.