How a natural compound from sea squirts combats cancer

1 / 1Trabectedin, an anti-cancer drug originally isolated from the sea squirt Ecteinascidia turbitana, is known to form cytotoxic DNA adducts. It is used to treat sarcomas and ovarian cancers and, in contrast to most antitumor agents, exerts its full activity in cells with active DNA repair. Credit: Kook Son et al

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. Precision medicine proves particularly beneficial in addressing cancers that have evolved to evade conventional treatments.

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. A collaborative effort led by Dr. Son Kook and Professor Orlando D. Schärer from the Center for Genomic Integrity within the Institute for Basic Science in South Korea, along with Dr. Vakil Takhaveev and Professor Shana Sturla from ETH Zurich, Switzerland, has illuminated the inner workings of this mysterious compound. Their research is published in the journal Nature Communications.

Using highly sensitive COMET chip assays to detect breaks formed in the genomes of cells, IBS researchers revealed trabectedin induces persistent breaks in the DNA of cancer cells. The researchers showed that these DNA breaks are only formed in cells with high levels of DNA repair, specifically those that operate a pathway called transcription-coupled nucleotide excision repair (TC-NER).

By Tom Leonhardt, Martin Luther University Halle-Wittenberg

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