RESUMO
This review explores the multifaceted relationship between dietary factors and breast cancer outcomes, focusing on unsaturated fats, the Mediterranean diet (MD), and other nutritional components. Breast cancer remains a significant global health concern, with lifestyle factors like diet playing a pivotal role in prevention and management. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Articles written in English and released between 2019 and 2024 were acceptable. We used pertinent search terms such as "unsaturated fats", "Mediterranean diet", "breast cancer", and "nutrition" to perform searches in PubMed, PubMed Central (PMC), EBSCOhost, and grey literature such as Google Scholar. After screening, 11 of the 479 original papers were chosen and included in the final review. These include cross-sectional analysis and systematic review, cohort study, narrative review, systematic review and meta-analysis, case-control study, randomized controlled trials (RCTs), and cross-sectional study. Key findings suggest that adherence to the MD correlates with improved quality of life measures and reduced mortality rates among women with breast cancer, particularly in older age groups. The diet's emphasis on antioxidant-rich foods, anti-inflammatory compounds, and healthy fats contributes to these observed benefits. Specific unsaturated fats, notably omega-3 polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), demonstrate anti-cancer properties by modulating cancer cell behavior and enhancing treatment responses. Biomarkers associated with the MD, such as ß-carotene and lycopene, serve as indicators of dietary compliance and potential risk reduction. Furthermore, components found in olive oil, including polyphenols and monounsaturated fatty acids, exhibit promising effects in preventing breast cancer by exerting antioxidant and anti-proliferative actions. Other dietary factors like calcium, legumes, fruits, and vegetables also play a role in reducing breast cancer risk and improving survival rates. This review underscores the importance of dietary interventions in optimizing outcomes for breast cancer patients and highlights the need for further research to elucidate underlying mechanisms and refine dietary recommendations.
RESUMO
Triple negative breast cancer (TNBC) accounts for over 30% of all breast cancer (BC)-related deaths, despite accounting for only 10% to 15% of total BC cases. Targeted therapy development has largely stalled in TNBC, underlined by a lack of traditionally druggable addictions like receptor tyrosine kinases (RTKs). Here, through full genome CRISPR/Cas9 screening of TNBC models, we have uncovered the sensitivity of TNBCs to the depletion of the ubiquitin-like modifier activating enzyme 1 (UBA1). Targeting UBA1 with the first-in-class UBA1 inhibitor TAK-243 induced unresolvable endoplasmic reticulum (ER)-stress and activating transcription factor 4 (ATF4)-mediated upregulation of proapoptotic NOXA, leading to cell death. c-MYC expression correlates with TAK-243 sensitivity and cooperates with TAK-243 to induce a stress response and cell death. Importantly, there was an order of magnitude greater sensitivity of TNBC lines to TAK-243 compared to normal tissue-derived cells. In five patient derived xenograft models (PDXs) of TNBC, TAK-243 therapy led to tumor inhibition or frank tumor regression. Moreover, in an intracardiac metastatic model of TNBC, TAK-243 markedly reduced metastatic burden, indicating UBA1 is a potential new target in TNBC expressing high levels of c-MYC.