BRCA1 and BRCA2 mutations cause breast and ovarian cancers. Moreover, GWAS studies have identified other more common, modest risk variants for both cancers. Environmental and lifestyle factors, including pregnancy and oral contraceptive use, also influence the onset and severity of these cancers. How genetic and non-genetic factors and ancestry affect cancer susceptibility, prevention, and treatment outcomes in subjects from South Texas remains to be explored. We will investigate the genetic and epidemiological risk factors associated with breast and ovarian oncogenesis in the underserved population of our catchment area. We will also develop induced pluripotent cell (iPSC) organoid models o...

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BRCA1 and BRCA2 mutations cause breast and ovarian cancers. Moreover, GWAS studies have identified other more common, modest risk variants for both cancers. Environmental and lifestyle factors, including pregnancy and oral contraceptive use, also influence the onset and severity of these cancers. How genetic and non-genetic factors and ancestry affect cancer susceptibility, prevention, and treatment outcomes in subjects from South Texas remains to be explored. We will investigate the genetic and epidemiological risk factors associated with breast and ovarian oncogenesis in the underserved population of our catchment area. We will also develop induced pluripotent cell (iPSC) organoid models of breast and fallopian tube tissues (precursor cell types for breast and ovarian cancers, respectively) and conduct CRISPR interference screens of genetic drivers to define the role of gene mutations and risk variants in cancer development and progression. With institutional colleagues and resources accorded to our new Center for Inherited Oncogenesis that I will direct, my team will: (1) Define new synthetic lethality relationships of genes that function in DNA repair, replication fork protection, and cellular mutagenesis associated with BRCA mutations; (2) Elucidate the impact of genetic modifiers on cancer pathogenesis and drug sensitivity; and (3) Leverage available infrastructure to help drive the development of new cancer therapeutics. Our endeavors will synergize with the research programs of our cadre of NCI and CPRIT funded colleagues, who are leaders in elucidating the mechanisms of salient DNA repair and tumor suppression pathways, many of whom have developed small molecule inhibitors that could become the next generation of therapeutics against breast and ovarian cancers. I expect our endeavors to help prevent and treat breast and ovarian cancers in South Texas, and to also serve as the model for our systematic efforts to tackle similar issues for other cancer types.

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