Unraveling the molecular mechanisms of early-onset breast cancer

Background Female breast cancer (BC) has surpassed lung cancer as the most commonly diagnosed cancer, with 2.3 million new cases. In addition, there has been a concerning rise in early-onset cancer cases (= 50 years old) in recent years. Aging, a primary risk factor for cancer, shares several key characteristics with cancer, including genomic instability and chronic inflammation. Understanding the interplay between microRNAs (miRs), cancer, and aging could lead to identify biomarkers for cancer predisposition and developing targeted therapies. Hypothesis Our hypothesis posits that early-onset BC patients exhibit accelerated biological aging in mammary tissue, potentially contributing to early tumor onset. Given the role of non-coding RNAs (ncRNAs) in aging and cancer processes, we propose that miRs may drive these accelerated aging features. Aims Our objectives are to (1) identify advanced biological aging traits in young BC patients compared to older individuals, (2) explore molecular pathways, particularly involving miRs, in young BC patients, (3) identify miRs as potential biomarkers for cancer predisposition in young women, and (4) investigate miR-based therapies and aging-related drugs to improve outcomes in young BC patients. Experimental Design Our experimental plan includes assessing aging traits in young normal and luminal A BC cells, investigating the effects of an aging microenvironment on BC progression, conducting biological and molecular investigations using xenotransplants in mice, and evaluating the potential of aging-related miRs as biomarkers and therapeutic targets. Expected Results We anticipate uncovering aging traits in young individuals, elucidating miR-mediated pathways in young BC patients, identifying miRs as potential biomarkers, and exploring miR-based therapies and aging-related drugs to enhance clinical outcomes in young BC patients. Impact On Cancer This research will shed light on the molecular mechanisms of early-onset BC development linked to accelerated aging driven by miRs in tumor and stromal cells, potentially leading to diagnostic, prognostic, and therapeutic advancements for clinical translation.