Immunocompetent C57BL/6 syngeneic mouse ovarian cancer models with defined genetic alterations.

Abstract

Ovarian cancer remains one of the deadliest gynecologic cancers globally, with limited progress in early detection and treatment. Syngeneic mouse ovarian cancer cell lines, derived from immunocompetent mice, have become essential tools for studying ovarian cancer biology and assessing novel therapies. With the rise of immunotherapies such as immune checkpoint inhibitors and cancer vaccines, these syngeneic models are critical for preclinical studies within the context of an intact immune system. The availability of diverse syngeneic ovarian cancer models ensures that research captures the full spectrum of human ovarian cancer variability, including variations in genetic mutations, signaling pathways, tumor antigenicity, and molecular subtypes. Here, we report the development and characterization of a panel of syngeneic ovarian cancer cell lines with defined combinations of initiating genetic alterations, such as TP53 deficiency, Hras mutation, and overexpression of Myc and Cyclin E. The Introduction of one or two oncogene drivers resulted in TP53-/- cell transformation and growth in nude and immunocompetent syngeneic C57BL/6 mice. Intraperitoneal tumors grew with high penetrance and had a wide metastatic distribution and concurrent ascites, which closely resembles the clinical picture of human serous ovarian cancer.