The complex signaling network within the breast tumor microenvironment is crucial for its growth, metastasis, angiogenesis, therapy escape, stem cell maintenance, and immunomodulation. An array of secretory factors and their receptors activate downstream signaling cascades regulating breast cancer progression and metastasis. Among various signaling pathways, the EGFR, ER, Notch, and Hedgehog signaling pathways have recently been identified as crucial in terms of breast cancer proliferation, survival, differentiation, maintenance of CSCs, and therapy failure. These receptors mediate various downstream signaling pathways such as MAPK, including MEK/ERK signaling pathways that promote common pro-oncogenic signaling, whereas dysregulation of PI3K/Akt, Wnt/β-catenin, and JAK/STAT activates key oncogenic events such as drug resistance, CSC enrichment, and metabolic reprogramming. Additionally, these cascades orchestrate an intricate interplay between stromal cells, immune cells, and tumor cells. Metabolic reprogramming and adaptations contribute to aggressive breast cancer and are unresponsive to therapy. Herein, recent insights into the novel signaling pathways operating within the breast TME that aid in their advancement are emphasized and current developments in practices targeting the breast TME to enhance treatment efficacy are reviewed.
乳腺肿瘤微环境中的复杂信号网络对其生长、转移、血管生成、治疗逃逸、干细胞维持及免疫调节至关重要。多种分泌因子及其受体通过激活下游信号级联反应，调控乳腺癌的进展与转移。在众多信号通路中，EGFR、ER、Notch和Hedgehog信号通路近期被证实对乳腺癌增殖、存活、分化、癌症干细胞维持及治疗失败具有关键作用。这些受体介导多种下游信号通路，如MAPK通路中的MEK/ERK信号通路可促进常见的促癌信号传导，而PI3K/Akt、Wnt/β-catenin和JAK/STAT通路的失调则会激活耐药性、癌症干细胞富集及代谢重编程等关键致癌事件。此外，这些信号级联反应协调了基质细胞、免疫细胞与肿瘤细胞之间复杂的相互作用。代谢重编程与适应性改变导致乳腺癌侵袭性增强并对治疗产生抵抗。本文重点阐述了乳腺肿瘤微环境中促进癌症进展的新型信号通路的最新研究进展，并综述了当前针对乳腺肿瘤微环境以提高治疗效能的策略发展。
Molecular Insights on Signaling Cascades in Breast Cancer: A Comprehensive Review
肿瘤(癌症)患者之家