24/09/2026
Promising new research on overcoming cancer drug resistance.
A new study published in Science Advances describes CS18, an experimental compound designed to inhibit TopBP1, a protein involved in several pathways that help cancer cells survive treatment.
Researchers found that CS18 disrupted cancer-promoting TopBP1 signaling, reduced MYC-related activity, restored mechanisms involved in cancer cell death, and showed activity across several cancer types.
One of the most interesting findings was its effect when combined with existing cancer treatments. CS18 enhanced the effectiveness of PARP inhibitors and restored sensitivity to osimertinib in lung cancer cells that had become resistant to the drug. In animal models, the combination also reduced tumor growth.
The results suggest that targeting TopBP1 could potentially provide a new strategy for overcoming treatment resistance and improving existing cancer therapies.
The research is still preclinical, and CS18 will require further testing before its safety and effectiveness in patients can be determined.
Paper:
https://www.science.org/doi/10.1126/sciadv.aeg1996
Figure 1 shows that the compounds 3B6, 4B4, and 4B5 attach to the cancer-related protein TopBP1 and interfere with some of its interactions. 4B4 and 4B5 were designed as modified versions of 3B6. They bind to a specific part of TopBP1 and block TopBP1 from interacting with other proteins. In breast and ovarian cancer cells, these compounds increased apoptosis, or programmed cancer cell death. They did not cause the same effect in the non-cancerous liver cells tested. 4B4 and 4B5 also reduced the ability of breast cancer cells to survive and grow into colonies.
In short: these compounds block TopBP1 activity and cause certain cancer cells to die or stop growing.
