Targeting The Mammary Stem And Progenitor Cell Population To Prevent Er+ Breast Cancer
Estrogen receptor positive (ER+) breast cancer (BCa) is the most commonly occurring BCa subtype (>70%). Though survival rates are >95% due to improvements in treatment strategies, the incidence of disease continues to rise despite current risk reducing/preventative strategies in place. One prevention strategy offered to women at high risk of ER+ BCa is aimed at modulating the ER activity through medication. However, the only chemopreventive available to both pre- and post-menopausal women has side effects that unfavourably reduce its uptake by patients. In order to overcome the side effect profiles of standard of care preventatives, we are interested in developing a mammary stem/progenitor cell targeted preventative. We have shown that the proportion of a particular stem/progenitor cell population changes in response to various reproductive risk modulators that increase or decrease risk of developing ER+ BCa, suggesting a potential cancer cell of origin that can be an adequate drug target prior to tumour development. Future work hopes to expand on this evidence by investigating the genomic (RNAseq and ATACseq) and functional changes occurring in these cells under various risk modulators of ER+ BCa and the effects of next generation Selective Estrogen Receptor Degraders (SERDs) compared to standard of care preventative treatments in our mouse models of ER+ BCa. In understanding how these cell subsets respond to these treatments we hope to elucidate potential molecular pathways that can be targeted for the prevention of ER+ BCa