Targeting hedgehog-driven mechanisms of drug-resistant cancers

Frontiers in Molecular Biosciences

Molecular Biosciences

Natalie E. Bennett¹  Jade S. Miller²  Julie A. Rhoades³ 

[1] Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States;Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, United States;Department of Veterans Affairs, Nashville VA Medical Center, Tennessee Valley Healthcare System, Nashville, TN, United States;Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, United States;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;Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, United States;Department of Veterans Affairs, Nashville VA Medical Center, Tennessee Valley Healthcare System, Nashville, TN, United States;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;Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, United States;Department of Veterans Affairs, Nashville VA Medical Center, Tennessee Valley Healthcare System, Nashville, TN, United States;Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, United States;

关键词: cancer;    chemotherapy;    resistance;    hedgehog;    Gli;   

DOI  :  10.3389/fmolb.2023.1286090

 received in 2023-08-30, accepted in 2023-10-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Miller, Bennett and Rhoades.