Asset Details
Do you wish to reserve the book?
Targeting NG2 relieves the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitors
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Targeting NG2 relieves the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitors
Do you wish to request the book?
Targeting NG2 relieves the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitors
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Targeting NG2 relieves the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitors
2024
Overview
BRAF
V600E
represents a constitutively active onco-kinase and stands as the most prevalent genetic alteration in thyroid cancer. However, the clinical efficacy of small-molecule inhibitors targeting
BRAF
V600E
is often limited by acquired resistance. Here, we find that nerve/glial antigen 2 (NG2), also known as chondroitin sulfate proteoglycan 4 (CSPG4), is up-regulated in thyroid cancers, and its expression is increased with tumor progression in a
BRAF
V600E
-driven thyroid cancer mouse model. Functional studies show that NG2 knockout almost does not affect tumor growth, but significantly improves the response of BRAF-mutant thyroid cancer cells to BRAF inhibitor PLX4720. Mechanistically, the blockade of ERK-dependent feedback by BRAF inhibitor can activate receptor tyrosine kinase (RTK) signaling, causing the resistance to this inhibitor. NG2 knockout attenuates the PLX4720-mediated feedback activation of several RTKs, improving the sensitivity of BRAF-mutant thyroid cancer cells to this inhibitor. Based on this finding, we propose and demonstrate an alternative strategy for targeting NG2 to effectively treat BRAF-mutant thyroid cancers by combining multiple kinase inhibitor (MKI) Sorafenib or Lenvatinib with PLX4720. Thus, this study uncovers a new mechanism in which NG2 contributes to the resistance of BRAF-mutant thyroid cancer cells to BRAF inhibitor, and provides a promising therapeutic option for BRAF-mutant thyroid cancers.
Publisher
Springer International Publishing,Springer Nature B.V
Subject
/ antigens
/ Biomedical and Life Sciences
/ Cancer
/ Chondroitin Sulfate Proteoglycans
/ Drug Resistance, Neoplasm - drug effects
/ Drug Resistance, Neoplasm - genetics
/ Feedback
/ Humans
/ Kinases
/ Mice
/ Mutants
/ Mutation
/ Original
/ Phenylurea Compounds - pharmacology
/ Phenylurea Compounds - therapeutic use
/ Protein Kinase Inhibitors - pharmacology
/ Protein-tyrosine kinase receptors
/ Proto-Oncogene Proteins B-raf - antagonists & inhibitors
/ Proto-Oncogene Proteins B-raf - genetics
/ Proto-Oncogene Proteins B-raf - metabolism
/ receptor protein-tyrosine kinase
/ Thyroid
/ Thyroid Neoplasms - drug therapy
/ Thyroid Neoplasms - genetics
/ Thyroid Neoplasms - metabolism
/ Thyroid Neoplasms - pathology
/ Tumors
/ Tyrosine
