由于癌症固有的细胞可塑性，获得治疗耐药性仍然是患者护理的最大障碍之一。在许多患者中，幸存的癌细胞亚群继续增殖或转移，这通常是细胞信号传导和转录途径发生显着改变的结果。一个值得注意的例子是 Hedgehog (Hh) 信号通路，它是多种癌症亚型的驱动因素，并在多种恶性肿瘤中因治疗而异常激活。这篇综述将总结该领域目前对 Hh 信号在耐药性中所发挥的多种作用的理解，并将包括 Gli 蛋白的非典型激活、促进化疗耐受的基因扩增、hedgehog 靶向药物的使用和工具化合物，以及我们对转录机制的了解仍然存在差距。版权所有 © 2023 Miller、Bennett 和 Rhoades。

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.Copyright © 2023 Miller, Bennett and Rhoades.