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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1545038
Onvansertib exhibits anti-proliferative and anti-invasive effects in endometrial cancer
Provisionally accepted
Nikita Sinha 1 Xiaochang Shen 1 Jennifer Haag 1
Shuning Chen 2 Haomeng Zhang 1 Catherine John 1 Wenchuan Sun 1 Michael Emanuele 3
Chunxiao Zhou 1*
Victoria Bae-Jump 1- 1 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, United States
- 2 Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China
- 3 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, Chapel Hill, United States
Polo-like kinase 1 (Plk1) is widely recognized as an oncogene that promotes cell proliferation by regulating cell division, DNA damage response, and genome stability and has been shown to be overexpressed in many cancers, including endometrial cancer. Targeting Plk1 by onvansertib has been shown to have antitumor activity in pre-clinical models of multiple cancers and is currently being evaluated in phase 1 and 2 clinical trials in cancer patients. In this study, we evaluated the potential anti-tumorigenic effects of onvansertib in endometrial cancer cells and the LKB1 fl/fl p53 fl/fl mouse model of endometrial cancer.Onvansertib inhibited cellular proliferation, caused G2 phase arrest, induced cellular stress and apoptosis, and inhibited cellular migration and invasion in endometrial cancer cells. Combined treatment with onvansertib and paclitaxel led to synergistic inhibition of cell proliferation. Onvansertib treatment for four weeks significantly reduced tumor growth in LKB1 fl/fl p53 fl/fl mice. Given these promising pre-clinical results, further studies are needed to evaluate the clinical translatability of onvansertib combined with paclitaxel as an effective treatment for endometrial cancer.
Keywords: Onvansertib, Polo-like kinase 1, endometrial cancer, Cell Proliferation, invasion, Apoptosis
Received: 13 Dec 2024; Accepted: 21 Feb 2025.
Copyright: © 2025 Sinha, Shen, Haag, Chen, Zhang, John, Sun, Emanuele, Zhou and Bae-Jump. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chunxiao Zhou, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, United States
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