Unraveling Cancer Pathogenesis: From Genetically Modified Mice to Stem Cell Pathology

摘要

Accurate mouse models of human cancer are expected to have common molecular mechanisms with human disease, show similar pathology of developed neoplasms, recapitulate human cancer progression, including its metastatic changes, and have therapeutic andhost immune responses resembling those in human patients. Advances in mouse and human genomics, as well as the development of sophisticated tools for manipulating the mouse genome, have greatly enhanced our ability to develop robust mouse models of human cancer by offering an opportunity to regulate gene functions in a conditional, spatial, temporal and cell type-specific manner For example, the majority of human high-grade serous ovarian carcinomas have alterations in pathways of tumor suppressor genes TP53 and RB1. While mice do not spontaneously develop such cancers, conditional Cre-loxP mediated inactivation of mouse Trp53 and Rb1 in the ovarian surface epithelium leads to aggressive carcinomas remarkably similar to human malignancies of the sametype