Uterine carcinosarcoma (CS) is a rare but aggressive endometrial malignancy. The incidence of CS has been increasing and is projected to continue to rise. African American women in particular have an increased incidence of CS and overall increased mortality related to endometrial cancer, underscoring known disparities in cancer care across racial and ethnic groups. Compared to other histologic subtypes, CS remains rare and understudied on a molecular and cellular basis, and under-represented in clinical trials. Therefore, current treatment therapies available for CS have been extrapolated from treatments used in other histologies of endometrial cancer, highlighting a significant need for effective treatment targeted at this subtype. Due to this paucity of data surrounding targeted therapies for CS, patients who are diagnosed with this aggressive and lethal cancer tend to have worse outcomes. We have developed a clinically relevant CS murine model by injecting human CS patient-derived organoids (PDO) from diverse ancestries into the endometrium of immunocompromised mice. Tumor progression in the mice was monitored with physical examination, PET/CT scan, contrast enhanced CT scan, ultrasound, and bioluciferase imaging. The tumor was established after three months, and the mice were sacrificed following the experiment. The diagnosis of invasive CS was confirmed by macroscopic and histologic analyses in the orthotopic model. Our orthotopic CS PDO transplantation model has many potential applications for studying tumor biology of CS in the pre-clinical setting. Future directions include trialing the efficacy of standard of care chemotherapy in the orthotopic model. Using this model, we aim to identify targeted therapy for CS and potentially advance to Phase I human clinical trials.

Citation Format: Megan Gorman, Divya Gowthaman, Arielle Katcher, Charlie Chung, Brian Yueh, Mali Barbi, Libia Garcia, Marina Frimer, Gary L. Goldberg, Semir Beyaz. A clinically relevant orthotopic endometrial carcinosarcoma mouse model using human patient-derived organoids [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B020.