Context: 

Recently, scientists at the Indian Association for the Cultivation of Science (IACS) in Kolkata have identified a promising new target for cancer treatment. 

More on the News: 

• This discovery could lead to more effective therapies, especially for patients resistant to current treatments.
• The research, published in The EMBO Journal 2024, that focusing on two important proteins, CDK1 and TDP1, could help create new cancer therapies.
• This approach suggests a potential combination therapy that could overcome resistance to existing cancer remedies.

Key Findings and Implications:

Novel Mechanism Unveiled: Researchers have found that cancer cells can resist current treatments by activating a specific enzyme called TDP1. 

• This activation helps the cancer cells survive despite the presence of drugs designed to kill them. This discovery opens up new possibilities for developing treatments aimed specifically at overcoming this resistance, targeting the mechanism that allows cancer cells to evade therapy.

Critical Proteins Identified: Two key proteins, Cyclin-dependent kinase 1 (CDK1) and Tyrosyl-DNA phosphodiesterase 1 (TDP1), were found to play crucial roles in DNA repair during cell division and in response to chemotherapy-induced damage.

Potential for Combination Therapy: The study suggests that using CDK1 inhibitors such as avotaciclib, alvocidib, roniciclib, riviciclib, and dinaciclib alongside Topoisomerase 1 (Top1) inhibitors could enhance cancer cell killing by disrupting DNA repair mechanisms and halting the cell cycle.

• Cancer cells often develop resistance to single-agent therapies through various mechanisms, such as modifications of DNA repair pathways or changes in cell cycle regulation. 
• By using both Top1 and CDK1 inhibitors together, this resistance can be overcome, reducing the likelihood of cancer cells surviving treatment.

Promising Therapy for Various Cancers: Although the study focused on human breast cancer cells, the combination of CDK1 inhibitors and Top1 inhibitors could offer significant benefits for patients with other cancers, including ovarian, colorectal, and small-cell lung cancers (SCLC). 

Ongoing Research: Further studies using animal models are underway to validate this approach and explore its full potential in clinical applications.

Way Forward: This research opens up new possibilities for developing more effective cancer treatments. By targeting both CDK1 and TDP1, scientists hope to overcome drug resistance and improve treatment outcomes for cancer patients.