Prof. Jaeyeon Kim
Indiana University School of Medicine
Ovarian Cancer: Role of Genes and Hormones
Metastasis is responsible for 90% of human cancer mortality. Yet it is challenging to model human cancer metastasis in vivo. We develop mouse models of high-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), the most common and deadliest human ovarian cancer type. These genetically engineered mouse models faithfully reproduce the peritoneal metastases of human HGSC with 100% penetrance. In these mice, tumors originate in the fallopian tube, spread to the ovary, and metastasize throughout the peritoneal cavity—notably to the omentum as well as the diaphragm, mesentery, and peritoneal membrane—inducing ascites and killing the mice. Besides the phenotypic similarity, mouse HGSCs also exhibit marked alterations in PI3K signaling, FOXM1 signaling, and homologous recombination pathway, the molecular signaling frequently dysregulated in human HGSC. Furthermore, mouse HGSCs display vast chromosomal instability and impaired DNA repair—prominent genomic features of human HGSC. Faithfully and reliably recapitulating the clinical and molecular characteristics of human HGSC, these mouse models reveal unexpected, crucial roles of ovarian steroid hormones in the development of HGSC. These provocative findings could serve as pivotal insights for reducing the risk of ovarian cancer in high-risk women carrying germline BRCA1/2 mutations.
Host : Prof. Facundo Fernandez