Scientists have identified a promising new target for cancer treatment by activating a DNA repair enzyme called TDP1, suggesting a combination therapy which could be a potential precision medicine especially for those resistant to current cancer remedies.
Existing anticancer drugs like Camptothecin, Topotecan, and Irinotecan target an enzyme crucial for DNA replication and transcription called Topoisomerase 1 (Top1). Cancer cells often develop resistance to such single-agent treatments and hence require alternate therapy methods.
In order to explore such alternative routes to treatment, scientists at the Indian Association for the Cultivation of Science (IACS),Kolkata, an autonomous institute of the Department of Science and Technology (DST)probed how cancer cells repair DNA during cell division and respond to chemotherapy that targets the enzyme Top1,often leading to drug resistance.
The research published in The EMBO Journal 2024 highlights two key proteins –Cyclin-dependent kinase 1 (CDK1) and Tyrosyl-DNA phosphodiesterase 1 (TDP1). The researchers led by Prof. Benu Brata Das found that cancer cells can counteract the effect of existing drugs by activating TDP1, a DNA repair enzyme, allowing them to survive.
While investigating how cancer cells repair DNA during cell division and respond to DNA damage induced by enzyme Topoisomerase 1 (Top1),the scientists discovered the critical roles of the proteins CDK1 and TDP1 that regulate the DNA repair process and repairs drug-induced trapped Top1 respectively.
