Baylor researchers report experimental drug CS18 blocks TopBP1, restores sensitivity to resistant cancer therapies and slows tumor growth in animal models.
Researchers at Baylor College of Medicine have created an experimental compound, CS18, that binds to the BRCT7/8 domain of topoisomerase II‑binding protein 1 (TopBP1). By disrupting this “biological switchboard,” CS18 reduces activity of cancer‑promoting proteins such as MYC, mutant p53, PLK1 and CIP2A, while increasing expression of growth‑inhibiting genes.
In laboratory tests CS18 decreased survival pathways in multiple cancer cell lines—including triple‑negative breast, ovarian, lung adenocarcinoma, lung squamous cell carcinoma and acute myeloid leukemia—and was less toxic to non‑cancerous cells. When combined with existing drugs such as PARP inhibitors or the EGFR inhibitor osimertinib, CS18 enhanced cancer‑cell killing and restored osimertinib sensitivity in previously resistant lung‑cancer cells. In animal models, the combination markedly reduced tumor growth without major weight loss or overt toxicity.
The authors propose that CS18 merits further development as a component of combination cancer therapies aimed at preventing or overcoming drug resistance. However, the reported data are limited to pre‑clinical cell‑culture and animal studies; clinical efficacy and safety in humans remain to be established.