A new drug that can potentially overcome cancer therapy resistance

Researchers at Baylor College of Medicine have developed a drug called CS18 that can potentially overcome cancer therapy resistance. The study, published in Science Advances, highlights the drug's ability to disrupt cancer cells' ability to survive treatment. Therapeutic resistance is a significant barrier to effective cancer treatment, as cancer cells often develop compensatory pathways that enable them to survive and relapse after therapy.

The researchers aimed to target a biological switchboard, Topoisomerase IIβ-binding protein 1 (TopBP1), which controls several cancer-driving pathways simultaneously. They identified a specific interaction within TopBP1, the BRCT7/8 domain, which can be manipulated to inhibit cancer-promoting activities. Through computer modeling and laboratory testing, they discovered compound 3B6, which was further modified to create CS18.

CS18 works by binding to BRCT7/8, reducing the cancer-promoting activities of MYC and mutant p53, impairing DNA repair proteins, and increasing cancer cell death. The drug showed promising results in various cancer cell types, including breast, ovarian, lung, and leukemia cancers, while exhibiting lower toxicity to noncancerous cells.

Furthermore, combining CS18 with existing cancer therapies, such as PARP inhibitors or osimertinib, enhanced their effectiveness, even restoring sensitivity in previously resistant lung cancer cells. The researchers propose CS18 as a potential candidate for further development as a drug to be included in combination treatments aimed at preventing or overcoming cancer drug resistance.