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Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer
Wang, Wang Shan, Danni Wang, Guanyi Mao, Xiongmin You, Wenjie Wang, Xiaolong Wang, Zijian
Wang, Wang
Shan, Danni
Wang, Guanyi
Mao, Xiongmin
You, Wenjie
Wang, Xiaolong
Wang, Zijian
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2024-01-29
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https://doi.org/10.1016/j.cellin.2024.100149
Abstract
Intravesical infusion of chemotherapeutics is highly recommended by several clinical guidelines for treating nonmuscle invasive bladder cancer (NMIBC). However, cytotoxic chemotherapeutics can cause a series of side effects, which greatly limits their application. Herein, a starvation therapy strategy was proposed, and elafibranor (ELA) was validated as a safe chemotherapeutic for NMIBC. The results showed that 20 μM ELA was sufficient to inhibit the proliferation and migration of bladder cancer cells and increase the level of intracellular reactive oxygen species (ROS). Furthermore, 2 mg/kg ELA treatment blocked the growth of primary tumors in an immunodeficient model by inhibiting proliferation and inducing apoptosis and improved the survival time of immunocompetent model mice. ELA treatment up to 10 mg/kg met the general safety requirements. We also established a patient-derived conditional reprogramming cell (CRC) model to assess the clinical translational potential of ELA. The antitumor effect and antitumor specificity of ELA treatment were confirmed. This work not only identified a promising chemotherapeutic for NMIBC but also provided a potential methodological system for drug discovery.
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Wang Wang, Danni Shan, Guanyi Wang, Xiongmin Mao, Wenjie You, Xiaolong Wang, Zijian Wang, Elafibranor emerged as a potential chemotherapeutic drug for non-muscle invasive bladder cancer, Cell Insight, Volume 3, Issue 1, 2024, 100149, ISSN 2772-8927, https://doi.org/10.1016/j.cellin.2024.100149. (https://www.sciencedirect.com/science/article/pii/S277289272400004X)
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Elsevier
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Cell Insight, Vol. 3, Iss. 1
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