State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Signal Transduct Target Ther. 2023 Aug 18;8(1):315. doi: 10.1038/s41392-023-01559-5.
The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor prognosis and even increased mortality. Understanding the integrative nature of HH signaling pathway has opened up the potential for new therapeutic targets for cancer. A variety of drugs have been developed, including small molecule inhibitors, natural compounds, and long non-coding RNA (LncRNA), some of which are approved for clinical use. This review outlines recent discoveries of HH signaling in tissue homeostasis and cancer and discusses how these advances are paving the way for the development of new biologically based therapies for cancer. Furthermore, we address status quo and limitations of targeted therapies of HH signaling pathway. Insights from this review will help readers understand the function of HH signaling in homeostasis and cancer, as well as opportunities and challenges of therapeutic targets for cancer.
过去十年中，我们对 Hedgehog（HH）信号通路在各种生物事件中的作用有了显著的认识。HH 信号通路通过涉及初级纤毛的复杂信号级联发挥其生物学效应。HH 信号通路在胚胎发育和组织稳态中具有重要功能。它在调节成体干细胞的增殖和分化中起着核心作用。重要的是，越来越明显的是，HH 信号通路与癌症患病率增加、恶性进展、预后不良甚至死亡率增加有关。了解 HH 信号通路的综合性质为癌症的新治疗靶点开辟了可能性。已经开发了多种药物，包括小分子抑制剂、天然化合物和长链非编码 RNA（LncRNA），其中一些已获准用于临床应用。本文综述了 HH 信号在组织稳态和癌症中的最新发现，并讨论了这些进展如何为癌症的新型基于生物学的治疗方法铺平道路。此外，我们还探讨了 HH 信号通路靶向治疗的现状和局限性。本文的见解将帮助读者了解 HH 信号在稳态和癌症中的功能，以及癌症治疗靶点的机遇和挑战。
