A new drug called CS18 may offer a way to overcome a major obstacle in cancer treatment: resistance to therapy. Researchers at Baylor College of Medicine have identified the compound as a potential breakthrough in blocking pathways that allow cancer cells to survive treatment, according to findings published in Science Advances. The drug targets TopBP1, a protein that acts as a “biological switchboard” for multiple cancer-promoting pathways, including those linked to MYC, mutant p53, and proteins that help tumors divide uncontrollably.
Cancer cells often develop resistance by activating alternative survival pathways when exposed to drugs. CS18 disrupts these defenses by binding to the BRCT7/8 domain of TopBP1, reducing the activity of proteins that repair DNA and promote tumor growth. In lab tests, the drug increased cancer cell death across multiple types, including triple-negative breast cancer, ovarian cancer, and lung cancer, while sparing healthy cells. When combined with existing therapies like PARP inhibitors or osimertinib, CS18 restored sensitivity in drug-resistant cells, significantly slowing tumor growth in animal models without major toxicity.
The research focused on BRCT7/8 because it interacts with key regulators of cancer progression. Unlike many treatments that target a single pathway, CS18 appears to interfere with multiple mechanisms at once. For example, it reduced the activity of MYC, a gene often overexpressed in cancers, and mutant p53, which can drive tumor growth when damaged. The drug also weakened DNA repair proteins, making cancer cells more vulnerable to standard therapies.
In practice, this could mean a shift toward combination treatments where CS18 is used alongside existing drugs to prevent resistance from developing in the first place. Patients who relapse after initial responses, often due to cancer cells adapting to treatment, might see improved outcomes if CS18 can reset their tumors’ sensitivity. The drug’s ability to work across different cancer types suggests it could address a broader range of tumors than many targeted therapies, though further testing is needed to confirm safety and efficacy in humans.
Development of CS18 began with a screen of thousands of chemical compounds, followed by iterative testing to refine its structure. The final version, CS18, emerged as the most effective at blocking BRCT7/8. The study was funded by grants from the National Institutes of Health, the Department of Defense, and other organizations, with the goal of advancing it toward clinical trials. The researchers emphasize that while preliminary results are promising, human testing will determine whether the drug can deliver durable responses in patients.
