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June 13, 2026Cancer Research CommunicationsOpen Access

Predicting clinical sensitivities of PDGFRA exon 18 mutations to imatinib and avapritinib to optimize gastrointestinal stromal tumor treatment

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Authors

HKHomma M. KhosroyaniATAlina TeuberATAjia Town

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Overview

Randomized trial predicts treatment response in gastrointestinal stromal tumors, suggesting improved therapy selection for patients.

Key Points

  • This study aims to determine which PDGFRA exon 18 mutations are sensitive to imatinib versus avapritinib in GISTs.
  • Analyzed over 1000 PDGFRA exon 18-mutant GIST cases
  • Used cell-based models to assess imatinib sensitivity based on amino acid composition
  • Validated findings with clinical data on patient responses to imatinib
  • 78% of mutations involve a key autoinhibitory residue at position 842
  • All hydrophobic amino acids except alanine confer resistance to imatinib
  • Patients with predicted exon 18 sensitive mutations had longer progression-free survival than those predicted to be resistant.

Cite This Study

Khosroyani et al. (2026) studied this question.

synapsesocial.com/papers/6a2cf45afaef96ed7f056a06https://doi.org/10.1158/2767-9764.crc-26-0093
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