Mutant p53 murine oviductal epithelial cells induce progression of high-grade serous carcinoma and are most sensitive to simvastatin therapy in vitro and in vivo.

High-grade serous carcinoma (HGSC) is the most common and aggressive subtype of epithelial ovarian cancer, characterized by gain-of-function TP53 mutations originating in the fallopian tube epithelium. Therapeutic intervention occurs at advanced metastatic disease, due to challenges in early-stage diagnosis, with common disease recurrence and therapy resistance despite initial therapy success. The mevalonate pathway is exploited by many cancers and is potently inhibited by statin drugs.

Comparative analysis of syngeneic mouse models of high-grade serous ovarian cancer.

Ovarian cancers exhibit high rates of recurrence and poor treatment response. Preclinical models that recapitulate human disease are critical to develop new therapeutic approaches. Syngeneic mouse models allow for the generation of tumours comprising the full repertoire of non-malignant cell types but have expanded in number, varying in the cell type of origin, method for transformation, and ultimately, the properties of the tumours they produce.

Gain-of-function p53 blocks apoptosis in a precursor model of ovarian high-grade serous carcinoma.

Ovarian high-grade serous carcinoma (HGSC) is a highly lethal malignancy for which early detection is a challenge and treatment of late-stage disease is ineffective. HGSC initiation involves exfoliation of fallopian tube epithelial (FTE) cells which form multicellular clusters called spheroids that colonize and invade the ovary. HGSC contains universal mutation of the tumour suppressor gene TP53.