Baylor scientists develop compound CS18 to overcome cancer drug resistance
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Scientists at Baylor College of Medicine have developed compound CS18, which disables cancer cells' ability to survive chemotherapy. The drug blocks multiple defense mechanisms, restoring sensitivity to standard cancer drugs. Tests show efficacy across five cancer types, including breast and lung cancer.
The Discovery
Researchers at Baylor College of Medicine screened thousands of chemical compounds using computer modeling and lab assays to find molecules that block the TopBP1 protein. They identified compound 3B6 and then modified it through multiple iterations to create CS18, the most effective candidate. The team was led by Dr. Wei-Chin Lin, who noted that therapeutic resistance is a major obstacle to long-term cancer treatment.
Mechanism of Action
CS18 binds to the BRCT7/8 domain, reducing the activity of cancer-promoting proteins MYC and mutant p53. This binding also makes DNA repair proteins less active, causing cancer cells to die more readily. Lin stated that CS18 further activates genes that inhibit uncontrolled cancer cell growth.
Preclinical Results
The compound proved effective in five cancer cell types: breast, ovarian, lung adenocarcinoma, squamous lung carcinoma, and acute myeloid leukemia. It showed lower toxicity to non-cancer cells and significantly reduced tumor growth in animal experiments without substantial weight loss or toxic signs. The researchers now propose CS18 for further development as part of a combination therapy to overcome drug resistance.
What's Next
The Baylor team will seek partners to advance CS18 into further drug development. It remains unclear when clinical trials in humans could begin.
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Baylor scientists develop compound CS18 to overcome cancer drug resistance
