Miller Jade S, Bennett Natalie E, Rhoades Julie A
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Pharmacology Training Program, Department of Pharmacology, Vanderbilt University, Nashville, TN, United States.
Front Mol Biosci. 2023 Oct 23;10:1286090. doi: 10.3389/fmolb.2023.1286090. eCollection 2023.
Due to the cellular plasticity that is inherent to cancer, the acquisition of resistance to therapy remains one of the biggest obstacles to patient care. In many patients, the surviving cancer cell subpopulation goes on to proliferate or metastasize, often as the result of dramatically altered cell signaling and transcriptional pathways. A notable example is the Hedgehog (Hh) signaling pathway, which is a driver of several cancer subtypes and aberrantly activated in a wide range of malignancies in response to therapy. This review will summarize the field's current understanding of the many roles played by Hh signaling in drug resistance and will include topics such as non-canonical activation of Gli proteins, amplification of genes which promote tolerance to chemotherapy, the use of hedgehog-targeted drugs and tool compounds, and remaining gaps in our knowledge of the transcriptional mechanisms at play.
由于癌症固有的细胞可塑性，获得对治疗的抗性仍然是患者护理面临的最大障碍之一。在许多患者中，存活的癌细胞亚群会继续增殖或转移，这通常是细胞信号传导和转录途径发生显著改变的结果。一个显著的例子是刺猬（Hh）信号通路，它是几种癌症亚型的驱动因素，并且在多种恶性肿瘤中因治疗而异常激活。本综述将总结该领域目前对Hh信号通路在耐药性中所起多种作用的理解，内容将包括Gli蛋白的非经典激活、促进化疗耐受性的基因扩增、刺猬靶向药物和工具化合物的使用，以及我们在转录机制方面仍存在的知识空白等主题。
