Experimental drug CS18 may overcome cancer resistance

Researchers at Baylor College of Medicine have developed an experimental drug called CS18 that disrupts a protein involved in multiple cancer survival pathways. In tests, it restored sensitivity to treatment in resistant lung cancer cells and slowed tumor growth in animal models. The findings, published in Science Advances, suggest CS18 could be a future therapy for resistant cancers.

The drug targets TopBP1's BRCT7/8 domain, a hub that interacts with proteins such as MIZ1, mutant p53, PLK1, and CIP2A. Researchers screened thousands of chemicals using computer modeling and laboratory experiments, identifying compound 3B6, then modified it to create CS18. The drug showed effects across five cancer types, including triple-negative breast cancer, ovarian cancer, lung adenocarcinoma, lung squamous cell carcinoma, and acute myeloid leukemia.

CS18 reduced cancer-promoting activities, weakened DNA repair processes, and increased tumor-suppressing gene activity while showing lower toxicity to non-cancerous cells. When combined with existing therapies like PARP inhibitors or osimertinib, the drug killed cancer cells more effectively than either treatment alone. In osimertinib-resistant lung cancer cells, CS18 restored drug sensitivity, and animal models demonstrated slowed tumor growth.