CS18 Overcomes Cancer Treatment Resistance

Researchers at Baylor College of Medicine have developed an experimental drug candidate named CS18 designed to overcome therapeutic resistance in cancer treatment by interfering with multiple tumor survival mechanisms simultaneously. Published in Science Advances on August 12, 2026, the study demonstrates that CS18 targets the topoisomerase II beta-binding protein 1 (TopBP1) switch BRCT7/8, effectively disrupting pathways driven by MYC and mutant p53 while reducing DNA repair activity. Led by corresponding author Dr. Weei-Chin Lin, the research team focused on TopBP1 because it acts as a biological control center interacting with several key regulators of cancer growth, including MIZ1, mutant p53, PLK1, and CIP2A. By blocking the BRCT7/8 region, CS18 weakens cancer cell defenses, increases the expression of tumor-suppressing genes, and lowers toxicity in non-cancerous cells during laboratory and animal studies. The strategic significance of CS18 lies in its ability to enhance existing cancer therapies rather than acting as a standalone treatment. Preclinical trials combining CS18 with PARP inhibitors and osimertinib showed significantly improved efficacy, successfully restoring drug sensitivity in lung cancer cells that had previously developed resistance to osimertinib without causing major animal weight loss or toxicity. Medical professionals and researchers can utilize these findings to advance combination therapies aimed at preventing clinical relapse in patients with triple-negative breast cancer, ovarian cancer, lung adenocarcinoma, lung squamous cell carcinoma, and acute myeloid leukemia. Future development will focus on clinical trials to validate CS18 safety and efficacy profiles in human oncology applications.