ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Myosin Light-Chain Kinase Inhibition Potentiates the Antitumor Effects of Avapritinib in PDGFRA D842V-Mutant Gastrointestinal Stromal Tumor.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- An endothelial-centered regulatory framework reveals context-dependent roles of MYLK in lung adenocarcinoma.Frontiers in immunology · 2026Article
- The Evolving Role of Second- and Third-Generation Tyrosine Kinase Inhibitors in Gastrointestinal Malignancies: Advances in Targeted Therapy with Sunitinib, Regorafenib, and Avapritinib.Journal of clinical medicine · 2026Review
- Investigating the role of MYLK2 in breast cancer prognosis and assessing its clinical application value.Scientific reports · 2025Article
- Patient-derived xenograft models of gastrointestinal stromal tumors provide a ready-to-use platform for translational research.Disease models & mechanisms · 2025Article
- Effect of forkhead box protein P2-mediated activation of myosin light-chain kinase on the invasion and migration of endometrial cancer cells.CytoJournal · 2025Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo create an in vivo model of PDGFRA D842V-mutant gastrointestinal stromal tumor (GIST) and identify the mechanism of tumor persistence following avapritinib therapy. EXPERIMENTAL
designWe created a patient-derived xenograft (PDX) of PDGFRA D842V-mutant GIST and tested the effects of imatinib, avapritinib, and ML-7, an inhibitor of myosin light-chain kinase (MYLK). Bulk tumor RNA sequencing and oncogenic signaling were evaluated. Apoptosis, survival, and actin cytoskeleton were evaluated in GIST T1 cells and isolated PDX cells in vitro. Human GIST specimens were analyzed for MYLK expression.
resultsThe PDX was minimally responsive to imatinib but sensitive to avapritinib. Avapritinib therapy increased tumor expression of genes related to the actin cytoskeleton, including MYLK. ML-7 induced apoptosis and disrupted actin filaments in short-term cultures of PDX cells and decreased survival in GIST T1 cells in combination with imatinib or avapritinib. Combined therapy with ML-7 improved the antitumor effects of low-dose avapritinib in vivo. Furthermore, MYLK was expressed in human GIST specimens.
conclusionsMYLK upregulation is a novel mechanism of tumor persistence after tyrosine kinase inhibition. Concomitant MYLK inhibition may enable the use of a lower dose of avapritinib, which is associated with dose-dependent cognitive side effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.