• Wesley C Burkett, Ziyi Zhao, Meredith A Newton, Wenchuan Sun, Boer Deng, SecordAngeles AlvarezAADivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University, Durham, NC., Chunxiao Zhou, and Victoria Bae-Jump.
• Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, NC.
• Ann. Med. 2023 Dec 1; 55 (1): 603614603-614.

PurposeUterine serous carcinoma (USC) exhibits worse survival rates compared to the endometrioid subtype, and there is currently no effective treatment options for recurrence of this disease after platinum-based chemotherapy. Activation of PIK3CA/AKT/mTOR signaling pathway is a common biological feature in USC.Materials And MethodsIpatasertib (IPAT) is an investigational, orally administered, ATP-competitive, highly selective inhibitor of pan AKT that has demonstrated anti-proliferative activity in a variety of tumor cells and tumor models. In this study, we used IPAT, carboplatin and their combination to investigate the anti-tumor activity in SPEC-2 and ARK-1 cells.ResultsOur results indicate that IPAT combined with carboplatin at low doses was more effective at reducing proliferation, inducing apoptosis and causing cellular stress than IPAT or carboplatin alone. In particular, inhibition of the PIK3CA/AKT/mTOR pathway and induction of DNA damage were involved in the synergistic inhibition by combination treatment of cell viability in USC cells treated with the combination. Furthermore, IPAT in combination with carboplatin significantly reduced cell adhesion and inhibited cell invasion.ConclusionsThese findings suggest that the combination of IPAT and carboplatin has potential clinical implications for developing new USC treatment strategies.

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