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| Study: Novel small molecule 5D4 disrupts several molecular pathways that lead to cancer growth |
Researchers at Baylor College of Medicine Achieve Remarkable Cancer Suppression
In a significant breakthrough, researchers at Baylor College of Medicine have identified a small molecule named 5D4 with the potential to suppress the growth of breast and ovarian cancers in animal models. This discovery opens new avenues for targeted cancer therapy, with promising implications for clinical use.
In their study published in the Proceedings of the National Academy of Sciences, researchers unveiled how 5D4 exerts its cancer-suppressing effects. It does so by binding to the TopBP1 protein within cancer cells, disrupting its interactions with multiple pathways that drive cancer growth. Moreover, when combined with another potent cancer inhibitor, talazoparib, 5D4 enhances the effectiveness of the anti-cancer activity, offering new hope for cancer patients.
Key Findings Transforming Cancer Therapy
The lead author of the study, Dr. Weei-Chin Lin, a distinguished professor at Baylor in medicine-hematology and oncology and molecular and cellular biology, as well as a member of Baylor's Dan L Duncan Comprehensive Cancer Center, explains the significance of their discovery: "Cancer development involves many steps of genetic alterations and signaling pathway deregulation. About 10 years ago, our team discovered that protein TopBP1 is at a convergent point of multiple cellular pathways involved in cancer growth and progression, making it a potential candidate for targeted cancer therapy."
Years of dedicated research, encompassing the screening of over 200,000 compounds and multiple rounds of structure-based compound optimization, have yielded promising results. Researchers have found that 5D4 effectively binds to TopBP1, inhibiting its ability to stimulate cancer-promoting molecular pathways. Notably, 5D4 also demonstrates the capacity to inhibit MYC activity in cancer—a particularly challenging target. This breakthrough may pave the way for indirect MYC targeting using TopBP1 inhibitors.
Precise and Targeted Action
Dr. Weei-Chin Lin continues, "The TopBP1 protein has multiple parts or domains that serve diverse functions within cells. 5D4 inhibits specific domains within TopBP1 that are involved in cancer progression without interfering with the protein's normal function in cell replication. The domains that 5D4 targets are responsible for regulating E2F1, mutant p53, MYC, and a process called homologous recombination. Thus, 5D4 shows anti-cancer activity without toxicity to normal tissues."
Enhanced Anti-Cancer Effect
The researchers also discovered that combining 5D4 with other compounds, such as PARP inhibitors, significantly amplifies the anti-cancer effect. This finding underscores the potential use of TopBP1 inhibitors as a targeted cancer therapy, offering a new dimension in the fight against cancer.
Promising Path Forward
Dr. Fang-Tsyr Lin, an associate professor at Baylor in medicine-hematology and oncology and a member of the Dan L Duncan Comprehensive Cancer Center, expresses excitement about the breakthrough: "It's very exciting to have found a TopBP1 inhibitor that really stops cancer growth in cells and in animal models in the lab. Our next step is to continue developing this compound for human testing, to optimize its anti-cancer effect in combination with other inhibitors and to minimize potential toxicities."
The dedicated efforts of Kang Liu, Lidija A. Wilhelms Garan, Helena Folly-Kossi, Yongcheng Song, and Shwu-Jiuan Lin, in addition to the authors, have been instrumental in bringing this promising research to light. The researchers are affiliated with Baylor College of Medicine and Taipei Medical University.
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