How a natural compound from sea squirts combats cancer

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Trabectedin, a promising drug derived from the sea squirt Ecteinascidia turbinata, has shown potential in combating cancers resistant to conventional treatments. However, its precise mechanism of action has remained elusive -- until now.

Numerous anti-cancer drugs function by targeting the DNA within cancerous cells, halting their proliferation. Yet, cancer cells occasionally develop mechanisms to repair the damage inflicted by these drugs, diminishing their effectiveness. Consequently, physicians are increasingly embracing a novel approach to cancer treatment known as precision medicine. This method involves selecting medications that precisely align with the unique attributes of an individual's cancer.

TC-NER is a vital mechanism that identifies DNA damage during transcription, initiating repair processes involving two endonucleases ERCC1-XPF and XPG. Trabectedin's DNA damage disrupts this process by allowing the initial incision by ERCC1-XPF but blocking the subsequent action by XPG, halting the TC-NER process. This disruption of the repair process leads to long-lasting DNA breaks that ultimately kill cancer cells.

"This incision by ERCC1-XPF creates a markable free hydroxyl group in the DNA, enabling us to sequence DNA and locate these breaks," explains Dr. Son.

Source: Healthcare Press (healthcarepress.net)

 

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