Kundu Shreyasi, P K Suresh
Department of Bio-medical Sciences, School of Biosciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India.
Curr Mol Med. 2025 Jul 4. doi: 10.2174/0115665240387430250508080548.
Fifteen to twenty percent of all cases of breast cancer are TNBC (triple negative breast cancer) and exhibit heterogenic features due to their diverse molecular characteristics. Additionally, their aberrant cell cycling behavior contributes to their metastatic capabilities and aggressive nature. TNBC is the only molecular subtype, which lacks the expression of hormone receptors, like estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). Hence, it is recalcitrant to hormone therapy. Also, the complex and evolving tumour microenvironment (TME) comprises blood vessels, stromal cells, immune cells, metabolic factors, extracellular matrix (ECM), and an integrated perspective of their interconnections as well as their variability with respect to TNBC progression needs to be comprehended for biomarker/druggable target(s) development and/or their validation. Such TME-based model systems can help us understand the relationship between the different TME components that affect tumour growth and metastasis. This review also catalogs biomarkers and TNBC behaviour within the TME. Also, this review discusses and analyses models that replicate various tumour subtypes that can be correlated with variability in treatment responses, thereby facilitating a better understanding of TNBC heterogeneity. Thus, by identifying biomarkers and constructing model systems, we can augment efforts to overcome treatment failure and poor outcomes in TNBC patients. These subtype-specific TNBC model systems, mirroring the intricacies of the TME, have the potential to provide a feasible and innovative approach to target TNBC cells. This review will facilitate the ongoing global efforts to develop efficacious and safe "tailor-made" drugs for TNBC patients.
所有乳腺癌病例中，15%至20%为三阴性乳腺癌（TNBC），由于其分子特征多样，呈现出异质性。此外，它们异常的细胞周期行为导致其具有转移能力和侵袭性。TNBC是唯一缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER-2）等激素受体表达的分子亚型。因此，它对激素治疗具有抗性。此外，复杂且不断演变的肿瘤微环境（TME）包括血管、基质细胞、免疫细胞、代谢因子、细胞外基质（ECM），为了生物标志物/可成药靶点的开发和/或验证，需要全面理解它们之间的相互联系以及它们在TNBC进展方面的变异性。这种基于TME的模型系统可以帮助我们理解影响肿瘤生长和转移的不同TME成分之间的关系。本综述还梳理了TME中的生物标志物和TNBC行为。此外，本综述讨论并分析了复制各种肿瘤亚型的模型，这些模型可与治疗反应的变异性相关联，从而有助于更好地理解TNBC的异质性。因此，通过识别生物标志物和构建模型系统，我们可以加大努力克服TNBC患者的治疗失败和不良预后。这些亚型特异性的TNBC模型系统反映了TME的复杂性，有可能为靶向TNBC细胞提供一种可行且创新的方法。本综述将促进全球正在进行的为TNBC患者开发有效且安全的“量身定制”药物的努力。
