Asset Details
Do you wish to reserve the book?
YY1 downregulation underlies therapeutic response to molecular targeted agents
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?
YY1 downregulation underlies therapeutic response to molecular targeted agents
Do you wish to request the book?
YY1 downregulation underlies therapeutic response to molecular targeted agents
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
YY1 downregulation underlies therapeutic response to molecular targeted agents
2024
Overview
During targeted treatment, oncogene-addicted tumor cells often evolve from an initial drug-sensitive state through a drug-tolerant persister bottleneck toward the ultimate emergence of drug-resistant clones. The molecular basis underlying this therapy-induced evolutionary trajectory has not yet been completely elucidated. Here, we employed a multifaceted approach and implicated the convergent role of transcription factor Yin Yang 1 (YY1) in the course of diverse targeted kinase inhibitors. Specifically, pharmacological perturbation of the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) pathway resulted in the downregulation of YY1 transcription, which subsequently resumed upon therapeutic escape. Failure to decrease YY1 subverted cytotoxic effects, whereas elimination of residual YY1 maximized anticancer efficacy and forestalled the emergence of drug resistance. Mechanistically, YY1 was uncovered to dictate cell cycle and autophagic programs. Immunohistochemical analysis on a wide spectrum of clinical specimens revealed that YY1 was ubiquitously expressed across lung adenocarcinomas and exhibited anticipated fluctuation in response to corresponding RTK/MAPK inhibition. These findings advance our understanding of targeted cancer management by highlighting YY1 as a determinant node in the context of genotype-directed agents.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 38/47
/ 38/91
/ 42/109
/ 82/80
/ Adenocarcinoma of Lung - drug therapy
/ Adenocarcinoma of Lung - genetics
/ Adenocarcinoma of Lung - metabolism
/ Adenocarcinoma of Lung - pathology
/ Animals
/ Antineoplastic Agents - pharmacology
/ Antineoplastic Agents - therapeutic use
/ Biomedical and Life Sciences
/ Down-Regulation - drug effects
/ Drug Resistance, Neoplasm - drug effects
/ Drug Resistance, Neoplasm - genetics
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humans
/ Kinases
/ Lung Neoplasms - drug therapy
/ Mice
/ Protein Kinase Inhibitors - pharmacology
/ Protein Kinase Inhibitors - therapeutic use
/ Protein-tyrosine kinase receptors
We currently cannot retrieve any items related to this title. Kindly check back at a later time.