Hilliard Aaron L, Russell Tanya D, Mendonca Patricia, Soliman Karam F A
Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA.
Center for Advancing Professional Excellence, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Cancers (Basel). 2025 Aug 27;17(17):2794. doi: 10.3390/cancers17172794.
Breast cancer remains a formidable global health challenge, with triple-negative breast cancer (TNBC) posing unique clinical complexities. Characterized by its aggressive nature and limited number of specific therapeutic targets, this breast cancer subtype disproportionately affects African American women, highlighting critical disparities in care. The tumor immune microenvironment (TIME) plays a critical role in breast cancer development and response to immunotherapy, and it is essential in fostering an immunosuppressive and pro-inflammatory niche. Inflammation, primarily mediated by the NF-κB signaling pathway and chemokine signaling, particularly involving CCL2, plays a pivotal role in TNBC progression and therapy resistance. This review describes some of the molecular mechanisms of polyphenols, which are naturally occurring compounds abundant in various dietary sources, and their potential use as therapeutic agents in the management of TNBC. Polyphenolic compounds have been described as modulating the TIME through the inhibition of tumor progression, immune evasion, and therapy resistance, due to their diverse bioactivities, including anti-inflammatory, antioxidant, and anticancer properties, making them attractive candidates for combating the aggressiveness of TNBC and addressing treatment disparities. Polyphenols, such as curcumin, gossypol, butein, epigallocatechin gallate, cardamonin, and resveratrol, have demonstrated efficacy in modulating several signaling pathways within the TIME, which are implicated in the progression of TNBC. This review highlights the potential effects of polyphenols on inflammatory cytokine release, programmed cell death ligand 1 (PD-L1) expression, which is associated with immune evasion by the host cell, and various intracellular signaling cascades, demonstrating their potential use in personalized therapeutic interventions for TNBC. This study also describes differential responses of TNBC cell lines to polyphenol treatment, highlighting the importance of considering genetic variability in therapeutic strategies, as well as the importance of the interaction of polyphenols with the gut microbiome, which may establish the bioavailability and effectiveness of these compounds toward therapeutic outcomes. Further preclinical and clinical studies are warranted to fully elucidate the therapeutic potential of polyphenols and translate these findings into clinical practice, thereby improving outcomes for patients with TNBC worldwide.
乳腺癌仍然是一项严峻的全球健康挑战，三阴性乳腺癌（TNBC）具有独特的临床复杂性。这种乳腺癌亚型具有侵袭性且特定治疗靶点数量有限，对非裔美国女性的影响尤为严重，凸显了护理方面的重大差异。肿瘤免疫微环境（TIME）在乳腺癌的发展和对免疫治疗的反应中起着关键作用，对于营造免疫抑制和促炎微环境至关重要。炎症主要由NF-κB信号通路和趋化因子信号介导，特别是涉及CCL2，在TNBC进展和治疗耐药中起关键作用。本综述描述了多酚类物质的一些分子机制，多酚是天然存在于各种饮食来源中的化合物，以及它们作为治疗剂在TNBC管理中的潜在用途。由于多酚类化合物具有多种生物活性，包括抗炎、抗氧化和抗癌特性，它们被描述为通过抑制肿瘤进展、免疫逃逸和治疗耐药来调节TIME，使其成为对抗TNBC侵袭性和解决治疗差异的有吸引力的候选物。姜黄素、棉酚、白杨素、表没食子儿茶素没食子酸酯、小豆蔻明和白藜芦醇等多酚类物质已证明在调节TIME内的多种信号通路方面具有功效，这些信号通路与TNBC的进展有关。本综述强调了多酚对炎症细胞因子释放、与宿主细胞免疫逃逸相关的程序性细胞死亡配体1（PD-L1）表达以及各种细胞内信号级联反应的潜在影响，证明了它们在TNBC个性化治疗干预中的潜在用途。本研究还描述了TNBC细胞系对多酚治疗的不同反应，强调了在治疗策略中考虑基因变异性的重要性，以及多酚与肠道微生物群相互作用的重要性，这可能决定这些化合物对治疗结果的生物利用度和有效性。需要进一步的临床前和临床研究来充分阐明多酚的治疗潜力，并将这些发现转化为临床实践，从而改善全球TNBC患者的治疗结果。
