College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.
Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, 261000, China.
Cell Commun Signal. 2024 Sep 9;22(1):432. doi: 10.1186/s12964-024-01812-6.
Breast cancer ranks as one of the most common malignancies among women, with its prognosis and therapeutic efficacy heavily influenced by factors associated with the tumor cell biology, particularly the tumor microenvironment (TME). The diverse elements of the TME are engaged in dynamic bidirectional signaling interactions with various pathways, which together dictate the growth, invasiveness, and metastatic potential of breast cancer. The Hedgehog (Hh) signaling pathway, first identified in Drosophila, has been established as playing a critical role in human development and disease. Notably, the dysregulation of the Hh pathway is recognized as a major driver in the initiation, progression, and metastasis of breast cancer. Consequently, elucidating the mechanisms by which the Hh pathway interacts with the distinct components of the breast cancer TME is essential for comprehensively evaluating the link between Hh pathway activation and breast cancer risk. This understanding is also imperative for devising novel targeted therapeutic strategies and preventive measures against breast cancer. In this review, we delineate the current understanding of the impact of Hh pathway perturbations on the breast cancer TME, including the intricate and complex network of intersecting signaling cascades. Additionally, we focus on the therapeutic promise and clinical challenges of Hh pathway inhibitors that target the TME, providing insights into their potential clinical utility and the obstacles that must be overcome to harness their full therapeutic potential.
乳腺癌是女性最常见的恶性肿瘤之一，其预后和治疗效果受肿瘤细胞生物学相关因素的影响较大，尤其是肿瘤微环境（TME）。TME 的多种成分与各种途径进行着动态的双向信号交互作用，共同决定了乳腺癌的生长、侵袭和转移潜能。Hedgehog（Hh）信号通路最初在果蝇中被发现，现已确定其在人类发育和疾病中发挥着关键作用。值得注意的是，Hh 通路的失调被认为是乳腺癌起始、进展和转移的主要驱动因素之一。因此，阐明 Hh 通路与乳腺癌 TME 中不同成分相互作用的机制对于全面评估 Hh 通路激活与乳腺癌风险之间的联系至关重要。这一理解对于设计针对乳腺癌的新型靶向治疗策略和预防措施也至关重要。在这篇综述中，我们阐述了目前对 Hh 通路失调对乳腺癌 TME 的影响的理解，包括相互交织的信号级联网络的复杂性和复杂性。此外，我们还关注了针对 TME 的 Hh 通路抑制剂的治疗潜力和临床挑战，深入探讨了它们的潜在临床应用和克服其充分治疗潜力所面临的障碍。
