Researchers at Baylor College of Medicine have made a significant breakthrough in the fight against breast and ovarian cancers. They have identified a small molecule, known as 5D4, which has shown the ability to suppress the growth of these cancers in animal models. The findings of their study were published in the Proceedings of the National Academy of Sciences, and they provide a compelling case for further investigation and development of this strategy for clinical use.
The researchers focused their efforts on identifying molecules that could bind to a protein called TopBP1, which plays a crucial role in promoting the growth of cancer cells. By disrupting the interactions between TopBP1 and various molecular pathways that contribute to cancer growth, 5D4 effectively inhibits the progression of breast and ovarian cancers. Additionally, when combined with another cancer inhibitor called talazoparib, 5D4 demonstrates an enhanced anti-cancer activity.
The discovery of 5D4 was the result of years of screening over 200,000 compounds and multiple rounds of structure-based compound optimization. The research team found that 5D4 not only binds to TopBP1 but also effectively inhibits its ability to stimulate several cancer-promoting molecular pathways. Notably, 5D4 has the ability to inhibit the activity of MYC, a notoriously challenging target in cancer treatment. This finding opens up new possibilities for indirectly targeting MYC with TopBP1 inhibitors.
One key advantage of 5D4 is its specific inhibition of certain domains within TopBP1 that are directly involved in cancer progression. This targeted approach ensures that the protein’s normal function in cell replication remains unaffected. The domains targeted by 5D4 regulate essential factors such as E2F1, mutant p53, MYC, and homologous recombination. Remarkably, 5D4 demonstrates anti-cancer activity without toxicity to normal tissues.
Dr. Fang-Tsyr Lin, one of the lead authors of the study, expressed excitement about the discovery of a TopBP1 inhibitor that effectively halts cancer growth both in cells and animal models. The next step for the research team is to continue developing 5D4 for human testing, optimizing its anti-cancer effects in combination with other inhibitors, and minimizing potential toxicities.
The study involved contributions from researchers Kang Liu, Lidija A. Wilhelms Garan, Helena Folly-Kossi, Yongcheng Song, and Shwu-Jiuan Lin, all affiliated with Baylor College of Medicine or Taipei Medical University.
This groundbreaking research received support from various sources, including NIH grants, Department of Defense grants, a Rivkin Center for Ovarian Cancer Pilot Award, and awards from T32CA174647 and T32GM136560. These funding sources underscore the significance of this study and its potential implications in the future of targeted cancer therapy.
In conclusion, the discovery of 5D4 as a small molecule inhibitor of TopBP1 represents a major step forward in the search for effective treatments for breast and ovarian cancers. Its ability to disrupt cancer-promoting pathways without harming normal tissues makes it a promising candidate for further development and clinical use. The research team is optimistic that their findings will pave the way for innovative treatment strategies and improved outcomes for patients with these challenging forms of cancer.
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1. Source: Coherent Market Insights, Public sources, Desk research
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