TP53 mutations in endometrial cancer contribute to clinically-relevant radiation resistance and highlight the potential for biomarker-driven radiosensitization strategies

Abstract

AbstractEndometrial cancer (EC) is the most common type of gynecologic malignancy in the United States, with over 65,950 new cases expected in 2022. Approximately 80% of cancer-related mortalities can be attributed to high-grade EC. Despite our ability to identify different biologic clusters of EC, we have yet to understand the functional and therapeutic impact of the key genomic alterations associated with poor prognosis EC and exploit this knowledge for therapeutic benefit. Given this, we set out to determine if and how common TP53 alterations found in high-grade ECs impact radiotherapy response, and if manipulation of this signaling pathway could be utilized for therapeutic intervention. Our work demonstrates that p53 signaling plays a significant role in radiotherapy response for EC and that leveraging this genomic data may allow us to exploit this pathway as a viable therapeutic target.