Disordered Differentiation of Tubal Epithelia: Setting the Stage for Neoplastic Transformation
Abstract
Most high-grade serous 'ovarian' cancers derive from cells lining the fallopian tube. Research by our laboratories and others has shown that in women with inherited mutations in genes such as BRCA1 that confer a high risk of ovarian cancer, fallopian tube cells fail to fulfill the normal cellular life cycle and become stuck in a state that is more prone to carcinogenesis. We believe that this failure of fallopian tube cells to properly differentiate explains, at least in part, why these women are more at risk of ovarian cancer. Similar changes also occur in post-menopausal women, albeit to a lesser extent. The overarching idea underlying this project is that if we can force these cancer-prone cells to complete the normal differentiation process that brings them into a less cancer prone state then we could effectively eliminate a woman's risk of ovarian cancer. Our long-term goal is to develop an oral drug that could be taken around the time of menopause to force the normal differentiation process to occur, and prevent ovarian cancer from occurring. This represents an entirely new paradigm for ovarian cancer prevention and is conceptually linked to the highly effective differentiation therapy for acute promyelocytic leukemia, which induces a complete remission in most patients due to forced differentiation of leukemic cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2023
- Accession Number
- AD1205230
Entities
People
- Kate Lawrenson
Organizations
- Cedars-Sinai Medical Center