Indian Scientists Develop New Therapy for Patients Resistant to Current Cancer Treatments

New Delhi: Scientists at the Indian Association for the Cultivation of Science (IACS), Kolkata, an autonomous institute under the Department of Science and Technology, have developed a groundbreaking therapy that could serve as precision medicine, particularly for patients resistant to existing cancer treatments.

Cancer cells frequently develop resistance to certain therapies, necessitating the search for alternative treatment approaches. The research team, led by Benu Brata Das, has identified a new target for cancer therapy by focusing on a DNA repair enzyme called Tyrosyl-DNA Phosphodiesterase 1 (TDP1), suggesting that combining therapies could be a more effective treatment strategy.

The team investigated how cancer cells repair their DNA during cell division and respond to chemotherapy, especially treatments targeting the Topoisomerase I (Top1) enzyme. Resistance to Top1 inhibitors often arises in cancer cells, complicating treatment. The research, published in The EMBO Journal, highlights the role of two key proteins in this process: Cyclin-dependent kinase 1 (CDK1) and TDP1.

The study reveals that cancer cells can resist the effects of current cancer drugs by activating TDP1, which repairs DNA damage and helps the cells survive. “Our research shows that CDK1 directly regulates TDP1, aiding cancer cells in repairing DNA breaks caused by Top1 inhibitors,” explained Das. By focusing on both CDK1 and TDP1, the team aims to overcome this resistance and improve the efficacy of cancer treatments.

To combat this resistance, the study suggests that combining CDK1 inhibitors—such as avotaciclib, alvocidib, roniciclib, riviciclib, and dinaciclib—with Top1 inhibitors could significantly enhance the ability to kill cancer cells. This dual-targeting approach would disrupt the cancer cells' DNA repair mechanisms and interrupt the cell cycle, making it harder for the cancer cells to survive.

“Cancer cells often develop resistance when treated with a single-agent therapy. By using a combination of CDK1 and Top1 inhibitors, we can more effectively target and destroy cancer cells,” Das added, stressing the potential of this combination therapy.

The findings present a promising new direction for precision medicine, especially for cancers that have become resistant to existing treatments. The combination of CDK1 and Top1 inhibitors offers a more comprehensive approach to eliminating cancer cells and could be an important step in advancing cancer treatment strategies.