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Collaborative Effort Sheds Light on Sea Squirt-Derived Drug’s Potential in Precision Cancer Treatment
Introduction: In the relentless battle against cancer, researchers have long sought innovative treatments capable of overcoming drug resistance and targeting the unique attributes of individual tumors. A recent collaborative effort led by scientists from the Center for Genomic Integrity within the Institute for Basic Science in South Korea and ETH Zurich in Switzerland has brought new hope in the form of trabectedin, a promising anti-cancer drug derived from the sea squirt Ecteinascidia turbinata.
Key Findings:
- Trabectedin’s Mechanism of Action: Utilizing highly sensitive high throughput COMET Chip assays, researchers discovered that trabectedin induces persistent breaks in the DNA of cancer cells. These breaks selectively target cells with high levels of DNA repair, specifically those utilizing the transcription-coupled nucleotide excision repair (TC-NER) pathway.
- Disruption of TC-NER: Trabectedin disrupts the TC-NER process by allowing initial DNA incision by ERCC1-XPF but blocking subsequent action by XPG, leading to long-lasting DNA breaks that ultimately kill cancer cells. This unique mechanism of action positions trabectedin as a potential treatment for cancers resistant to conventional therapies.
- Development of TRABI-Seq: Researchers developed a novel method called TRABI-Seq, which precisely identifies trabectedin’s action sites within tumor cell DNA. This breakthrough allows for the targeted evaluation of trabectedin’s efficacy in tumors with advanced DNA repair capabilities, often associated with elevated transcription levels due to oncogene activation.
Expert Insights:
- Dr. Son Kook (Center for Genomic Integrity, IBS): Dr. Son highlights the significance of trabectedin-induced DNA breaks and the development of TRABI-Seq in advancing precision cancer treatment.
- Professor Orlando D. Schärer (Center for Genomic Integrity, IBS): Professor Schärer emphasizes the potential of trabectedin in targeting drug-resistant cancers with highly active DNA repair capabilities, offering hope in the fight against treatment-resistant tumors.
Future Directions: The research team aims to further explore trabectedin’s efficacy in targeting tumors resistant to conventional therapies using TRABI-Seq. By identifying vulnerable cancers and developing trabectedin as a predictive marker and therapeutic option for precision treatment, researchers hope to expand treatment options for patients with drug-resistant cancer.
Conclusion: The groundbreaking research on trabectedin’s mechanism of action represents a significant advancement in the field of precision cancer treatment. With its ability to target drug-resistant tumors with highly active DNA repair mechanisms, trabectedin offers new hope for patients facing limited treatment options. As scientists continue to unravel the complexities of cancer biology, trabectedin stands poised to make a significant impact in the fight against treatment-resistant cancers.
