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Myosin Light-Chain Kinase Inhibition Potentiates the Antitumor Effects of Avapritinib in PDGFRA D842V-Mutant Gastrointestinal Stromal Tumor.

Author: AntonescuCristina R, DeMatteoRonald P, DoKevin, EtheringtonMark S, HannaAndrew, LiuMengyuan, ParamNesteene J, RossiFerdinand, TieniberAndrew, VitielloGerardo A, WangLaura, ZengShan, ZhangJennifer Q

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Overview

A patient-derived xenograft (PDX) of PDGFRA D842V-mutant gastrointestinal stromal tumor (GIST) was created to study the mechanism of tumor persistence following avapritinib therapy. Avapritinib therapy increased tumor expression of genes related to the actin cytoskeleton, including MYLK. MYLK inhibition may enable the use of a lower dose of avapritinib.
Paper Details　
Original Abstract of the Article :
PURPOSE: To create an in vivo model of PDGFRA D842V-mutant gastrointestinal stromal tumor (GIST) and identify the mechanism of tumor persistence following avapritinib therapy. EXPERIMENTAL DESIGN: We created a patient-derived xenograft (PDX) of PDGFRA D842V-mutant GIST and tested the effects of ima...See full text at original site
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引用元：
https://pubmed.ncbi.nlm.nih.gov/36971786

データ提供：米国国立医学図書館（NLM）

Myosin Light-Chain Kinase Inhibition: A New Strategy for Combating GIST

This study investigates the potential role of [myosin light-chain kinase (MYLK)] in the development of [gastrointestinal stromal tumor (GIST)] and its resistance to [tyrosine kinase inhibitors] such as [avapritinib]. The researchers discovered that MYLK is upregulated in GIST cells after avapritinib therapy, contributing to tumor persistence. The study also demonstrates that inhibiting MYLK using [ML-7] can enhance the antitumor effects of avapritinib, suggesting a new strategy for treating GIST, especially for those with [PDGFRA D842V] mutations.

MYLK Inhibition: A Potential Breakthrough in GIST Treatment

This study sheds new light on the role of MYLK in GIST development and resistance to tyrosine kinase inhibitors. The findings suggest that inhibiting MYLK could enhance the effectiveness of avapritinib, particularly for patients with PDGFRA D842V mutations. This research offers a potential breakthrough in GIST treatment, providing a new avenue for targeting tumor resistance and improving treatment outcomes.

GIST: A Challenging Cancer with Emerging Treatments

Gastrointestinal stromal tumor (GIST) is a challenging cancer that often develops resistance to conventional therapies. This study highlights the importance of understanding the mechanisms underlying tumor resistance to develop more effective treatment strategies. The findings suggest that MYLK inhibition, in combination with tyrosine kinase inhibitors, could offer a promising approach to combating GIST, especially for those with PDGFRA D842V mutations.

Dr.Camel's Conclusion

Imagine GIST cells as a stubborn desert fortress, resistant to the attacks of tyrosine kinase inhibitors. This study reveals a hidden weakness within the fortress: MYLK. By targeting MYLK with inhibitors like ML-7, we can potentially weaken the fortress and create a pathway for more effective treatments. This research offers a fascinating glimpse into the intricate world of cancer biology, reminding us that understanding the mechanisms of resistance is crucial for developing new therapies and improving patient outcomes.

Date :
  1. Date Completed 2023-06-02
  2. Date Revised 2023-12-02
Further Info :

Pubmed ID

36971786

DOI: Digital Object Identifier

NIHMS1888390

SNS
PICO Info
in preparation
Languages

English

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