Ovarian Cancer and Reproductive System Biology: A Harvard Stem Cell Institution Consortium

摘要

The dominant theme of the consortium is the discovery and functional analysis of genetic alterations and pathways that alter the normal self-renewal and differentiation of epithelial precursor populations and thereby produce cancer sustaining stem cells. Dominant aims include: 1) prioritizing candidates that emerge from The Cancer Genome Atlas (TCGA) through a series of functional studies; 2) testing for altered expression or function of gene candidates in human pathologic samples, with an emphasis on alterations in early stage lesions; 3) testing known genetic lesions and novel gene candidates for transformation of specific human target cells in vitro and validating the essential role of gene candidates in ovarian cancer stem cells; 4) developing genetically defined murine models of ovarian and germ cell cancers; 5) testing a novel genetic pathway involving Lin28A/B and the tumor suppressor microRNA let-7 for roles in ovarian and germ cell tumor initiation and maintenance; and 6) performing chemical-genetic screens for compounds that block the Lin28/let7 pathway. The long-term goal of the Consortium is to discover the specific links between gene alterations, target cells of transformation, and the genetic pathways that drive ovarian tumorigenesis to advance early diagnosis and treatment options.