"Oncogenic TRIM37 in TNBC: From Molecular Mechanism to New Functions"

Triple negative breast cancer (TNBC) accounts for approximately 10–15% of all breast cancer diagnoses, and it carries the worst prognosis among all breast cancer subtypes. Clinically, the leading causes of death in TNBC patients are attributed to its high chemoresistance and the rapid spread of metastasis. These two factors are more prevalent in younger women of African descent, who experience disproportionately higher tumor burden compared to other races. Although tumorigenic drivers of TNBC are numerous and varied, the drivers of metastatic transition and chemoresistance remain largely unknown. Here, I characterized TRIM37 function in driving an aggressive TNBC biology, revealing its critical role in chemoresistance and metastatic progression. Interestingly, TNBC affects younger Black women (BW), who experience significantly higher incidence and lower survival rates compared to White women (WW). I demonstrated TRIM37 as a genetic driver of racial disparities in TNBC. My results show that the risk allele of rs57141087 in BW increases TRIM37 expression via NRF1-mediated interactions. Together, my results reveal that TRIM37 is a potential predictive biomarker and therapeutic target for improving TNBC screening and treatment outcomes. My findings suggest that additional clinically relevant drivers of metastatic progression could exist, which could improve the likelihood of finding new treatments for TNBC patients. Therefore, future studies utilizing genome-wide genetic screens could be used toward this goal. Furthermore, new racially segregating variants associated with breast cancer risk could be identified using omics approaches. Based on my findings, future studies will focus on identifying new racially segregating genetic variants that could increase breast cancer risk.