Translational Reprogramming Drive Aggressive Triple-Negative Breast Cancer Phenotypes in Women of African Ancestry
Breast cancer does not affect all women equally. Black women (of African ancestry, WAA) are more likely to develop an aggressive form of breast cancer called triple- negative breast cancer (TNBC).
TNBC has no targeted treatments and is often diagnosed at younger ages and at more advanced stages in WAA compared to White women, even with equal access to health care. Researchers do not yet understand, at the molecular level, why WAA-TNBC is so aggressive.
Our research team at McMaster University has identified two important clues. First, WAA-TNBC tumours carry unique genetic changes (called copy-number variations, CNVs) that can alter chemical tags on DNA known as DNA methylation (DNAMet). These tags control which genes are switched on or off, and their disruption may activate aggressive cancer-promoting programs specific to WAA. Second, the expression of a gene called PWP2 is consistently elevated in WAA-TNBC and favours the ability of cancer cells to spread to vital organs.
This project addresses these two findings through coordinated studies. We will first map how WAA-specific CNVs interact with DNAMet to identify molecular signatures that drive aggressive TNBC in WAA. We will then investigate how PWP2 reprograms the cell’s protein-making machinery to selectively produce proteins that drive tumour spread and treatment resistance.
Together, these studies will help uncover the molecular basis of aggressive triple- negative breast cancer in Women of African ancestry and may reveal new targets for diagnosis and treatment that will benefit all women with aggressive TNBC, regardless of ethnicity.
