Simon Gayther, PhD
About Project
Identifying molecular targets to prevent transformation of P53 mutant serous tubal intraepithelial carcinomas
PROJECT SUMMARY
A central problem in the prevention and treatment of advanced high-grade serous ovarian cancer (HGSOC) is the lack of understanding of genetic mutations that occur in the earliest stages of disease development. Mutation in the p53 gene is the only genetic event shared among all HGSOCs and is the most recognized genetic event in precancerous lesions that develop from the fallopian tube. p53 acts as one of the most important “brakes” in cancer formation, because of its critical role in inhibiting cellular division and inducing cell death. But cancers require the accumulation of numerous genetic changes before they become lethal. Identifying the most important ‘sets’ of genetic changes in early stage cancer may provide opportunities to treat precancerous cells before they become too advanced to treat. In the current study, we hypothesize that by performing genomic and functional analysis of experimental models of fallopian tube cells engineered to carry p53 mutations (FT-p53 MUT cells) we can identify novel molecular targets that can be used for chemo-prevention of HGSOC. Genome editing is a new technology that enables us to test the function of thousands of genes to find those that are the most important in cancer development. In the current study, we plan to perform genome editing-based functional screening for 19,500 different genes in FT-p53MUT cells. The goal is to identify genes that collaborate with p53MUT in inducing the development of HGSOC. The ultimate goal is to identify novel molecules that represent clinical biomarkers and targets for chemo-prevention of HGSOC.
