Abstract Endometrial cancer (EC) is the most common gynecologic malignancy. However, progress in developing new therapeutic strategies has been limited by the lack of immunocompetent animal models that faithfully recapitulate human EC, including intact immune responses and the ability to form distant metastases. To address this gap, we developed an orthotopic, immunocompetent EC mouse model using the GFP-labeled mouse endometrial cancer cell line MECPK (Pten-deleted, Kras-activated). Following uterine abrasion, 50,000 MECPK cells were injected into the uterine lumen of recipient mice. Uterus tissues with EC were collected from mice at 4, 5, 6, and 8 weeks post-induction using a fluorescence-guided dissecting microscope. Samples were processed for hematoxylin and eosin (H0.001) and 8 weeks (133.16 ±12.98, p0.001), as well as in metastasis endometrial cancer in lung at 8 weeks (110.89 ±19.26, p0.001). These findings establish a robust immunocompetent orthotopic EC model that recapitulates primary tumor progression and distant metastasis, providing a valuable platform for mechanistic studies and preclinical evaluation of emerging therapies, including immunotherapy. This work was supported by NCI R01 CA264944 Citation Format: Keun Cheon Kim, Cassandra Schmidt, Eunhee M Jeong, Tae Hoon Kim, Jae-Wook Jeong. Development of an immunocompetent orthotopic mouse model recapitulating metastatic endometrial cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 201.
Kim et al. (Fri,) studied this question.