Chai Jian Yi, Sugumar Vaisnevee, Alshanon Ahmed F, Wong Won Fen, Fung Shin Yee, Looi Chung Yeng
School of Biosciences, Faculty of Health & Medical Sciences, Taylor's University, Subang Jaya 47500, Malaysia.
School of Medicine, Faculty of Health & Medical Sciences, Taylor's University, Subang Jaya 47500, Malaysia.
Cancers (Basel). 2021 Sep 23;13(19):4746. doi: 10.3390/cancers13194746.
Insight into cancer signaling pathways is vital in the development of new cancer treatments to improve treatment efficacy. A relatively new but essential developmental signaling pathway, namely Hedgehog (Hh), has recently emerged as a major mediator of cancer progression and chemoresistance. The evolutionary conserved Hh signaling pathway requires an in-depth understanding of the paradigm of Hh signaling transduction, which is fundamental to provide the necessary means for the design of novel tools for treating cancer related to aberrant Hh signaling. This review will focus substantially on the canonical Hh signaling and the treatment strategies employed in different studies, with special emphasis on the molecular mechanisms and combination treatment in regard to Hh inhibitors and chemotherapeutics. We discuss our views based on Hh signaling's role in regulating DNA repair machinery, autophagy, tumor microenvironment, drug inactivation, transporters, epithelial-to-mesenchymal transition, and cancer stem cells to promote chemoresistance. The understanding of this Achilles' Heel in cancer may improve the therapeutic outcome for cancer therapy.
深入了解癌症信号通路对于开发新的癌症治疗方法以提高治疗效果至关重要。一种相对较新但至关重要的发育信号通路，即刺猬信号通路（Hh），最近已成为癌症进展和化疗耐药性的主要介导因素。进化保守的Hh信号通路需要深入了解Hh信号转导的模式，这对于设计治疗与异常Hh信号相关癌症的新型工具提供必要手段至关重要。本综述将主要关注经典的Hh信号通路以及不同研究中采用的治疗策略，特别强调Hh抑制剂和化疗药物的分子机制及联合治疗。我们基于Hh信号在调节DNA修复机制、自噬、肿瘤微环境、药物失活、转运体、上皮-间质转化和癌症干细胞以促进化疗耐药性方面的作用来讨论我们的观点。对癌症中这一致命弱点的理解可能会改善癌症治疗的疗效。
