A clinically-relevant orthotopic endometrial carcinosarcoma mouse model using human patient-derived organoids

Katcher, Arielle, Chung, Charlie, Gorman, Megan, Yueh, Brian, Lyons, Scott, Merrill, Joseph, Garcia, Libia, Frimer, Marina, Goldberg, Gary L, Beyaz, Semir (2023) A clinically-relevant orthotopic endometrial carcinosarcoma mouse model using human patient-derived organoids. In: American Association for Cancer Research Annual Meeting 2023, 2023 Apr 14-19, Orlando, FL.

DOI: 10.1158/1538-7445.AM2023-34


Uterine carcinosarcoma (CS) is a rare but aggressive endometrial malignancy. Like the other subtypes of endometrial cancer, the incidence of CS has been increasing and it is projected to continue to rise. Additionally, there is racial disparity seen in African American women diagnosed with CS. African American women have an increased incidence of CS compared to other racial/ethnic groups. They also have an overall increased mortality related to endometrial cancer. Compared to other histologic subtypes of endometrial cancer, CS remains rare and understudied on a molecular and cellular basis. It remains under-represented in clinical trials. Therefore, the current therapies available for CS are extrapolated from those treatments used in the other subtypes of endometrial cancer. There is a paucity of data surrounding targeted therapies for CS resulting in worse outcomes for patients who are diagnosed with this aggressive and lethal cancer. We have developed a clinically relevant, orthotopic CS murine injection 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, and ultrasound. The tumor was established after three months and was visualized using various imaging techniques. The mice were sacrificed and the diagnosis of invasive CS was confirmed by macroscopic, histologic and genomic analyses. Our orthotopic CS PDO transplantation model has many potential applications for studying tumor biology and the response to treatment for CS in the pre-clinical setting. This may help identify targeted therapy for CS and potentially advance to Phase 1 human clinical trials.

Item Type: Conference or Workshop Item (Poster)
Subjects: Investigative techniques and equipment > cell culture > cancer organoids
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Beyaz lab
CSHL labs > Lyons lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 2023
Date Deposited: 19 Sep 2023 14:20
Last Modified: 19 Sep 2023 14:20
Related URLs:
URI: https://repository.cshl.edu/id/eprint/40904

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