Abstract Background: Syngeneic models of ovarian cancer enable assessments of therapeutics in the presence of the fully natural mouse immune system. Our laboratory recently developed high-grade serous ovarian cancer syngeneic models derived from spontaneous tumors from an Ovgp1-Trp53-R270H-Myc “OvTrpMyc” autochthonous model. These models were previously established to transcriptionally cluster with human high-grade serous ovarian cancers. Here, we describe progress in developing these models into rapid progression syngeneic models implantable into wild-type C57BL/6J mice. Methods: We focused on accelerating tumorigenesis of two autochthonous tumor model isolates: an ovary and fallopian tube isolate F318LOV, and a uterus isolate F319UT. To accomplish this acceleration, tumors acquired from an intraperitoneal passage in mice were again re-implanted in wild-type mice. Results: In the case of F318LOV, time to lethal cancer development was shortened from 132 days from the original syngeneic tumor formation experiment to an average of 47 days (intraperitoneal route) or 44 days to reach 100mm³ by subcutaneous route. For the uterine isolate, which transcriptionally clusters with uterine serous cancer, an aggressive form of endometrial cancer which is also p53-mutant and MYC-high, the F319UT cell line lethality averaged 87 days in wild-type mice. There is potential for immune-sensation of the cancer cells, as parallel injections into the transgenic mice used to initially create these syngeneic lines yielded more rapid tumor progression: 60 days. To further accelerate tumor formation, wild-type isolates were expanded and re-injected intraperitoneally. This formed an ultra-rapid progression model, in which mice required euthanasia due to tumor burden within 15 days. Conclusion: These two syngeneic models, one of high-grade serous ovarian cancer, one of uterine serous carcinoma, are available for the gynecologic cancer community for testing new therapies and biology in immune-competent settings in inexpensive C57BL/6J mice. Citation Format: Heather R. Ghent, Madison Clark, Amy Rees, Joe R. Delaney. Syngeneic intraperitoneal mouse models of p53-mutant Myc-amplified high-grade serous ovarian cancer and uterine serous carcinoma accelerated by serial mouse inoculations abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85 (18Suppl): Abstract nr A062.
Ghent et al. (Fri,) studied this question.