Background

Breast cancer (BC), the second most common cause of cancer-related deaths, remains a significant threat to the health and wellness of women worldwide. The tumor microenvironment (TME), comprising cellular components, such as cancer-associated fibroblasts (CAFs), immune cells, endothelial cells and adipocytes, and noncellular components such as extracellular matrix (ECM), has been recognized as a critical contributor to the development and progression of BC. The interplay between TME components and cancer cells promotes phenotypic heterogeneity, cell plasticity and cancer cell stemness that impart tumor dormancy, enhanced invasion and metastasis, and the development of therapeutic resistance. While most previous studies have focused on targeting cancer cells with a dismal prognosis, novel therapies targeting stromal components are currently being evaluated in preclinical and clinical studies, and are already showing improved efficacies. As such, they may offer better means to eliminate the disease effectively.

Conclusions

In this review, we focus on the evolving concept of the TME as a key player regulating tumor growth, metastasis, stemness, and the development of therapeutic resistance. Despite significant advances over the last decade, several clinical trials focusing on the TME have failed to demonstrate promising effectiveness in cancer patients. To expedite clinical efficacy of TME-directed therapies, a deeper understanding of the TME is of utmost importance. Secondly, the efficacy of TME-directed therapies when used alone or in combination with chemo- or radiotherapy, and the tumor stage needs to be studied. Likewise, identifying molecular signatures and biomarkers indicating the type of TME will help in determining precise TME-directed therapies.

中文翻译：

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肿瘤微环境作为乳腺癌干性和治疗耐药性的驱动因素：新挑战和治疗机遇

背景

乳腺癌 (BC) 是癌症相关死亡的第二大常见原因，仍然对全世界女性的健康构成重大威胁。肿瘤微环境 (TME) 包括细胞成分，如癌症相关成纤维细胞 (CAF)、免疫细胞、内皮细胞和脂肪细胞，以及非细胞成分，如细胞外基质 (ECM)，已被认为是发展的关键因素和 BC 的进展。TME 成分和癌细胞之间的相互作用促进了表型异质性、细胞可塑性和癌细胞干性，从而赋予肿瘤休眠、增强的侵袭和转移以及治疗抗性的发展。虽然之前的大多数研究都集中在针对预后不佳的癌细胞，针对基质成分的新疗法目前正在临床前和临床研究中进行评估，并且已经显示出改善的疗效。因此，它们可能提供更好的方法来有效地消除这种疾病。

结论

在这篇综述中，我们关注 TME 作为调节肿瘤生长、转移、干性和治疗耐药性发展的关键参与者的不断发展的概念。尽管在过去十年中取得了重大进展，但几项专注于 TME 的临床试验未能证明对癌症患者有希望的有效性。为了加快 TME 导向疗法的临床疗效，对 TME 的更深入了解至关重要。其次，TME导向疗法单独使用或与化疗或放疗联合使用时的疗效，以及肿瘤分期需要研究。同样，识别指示 TME 类型的分子特征和生物标志物将有助于确定精确的 TME 导向疗法。