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A literature review and database of how the primary KIT/PDGFRA variant of a gastrointestinal stromal tumour predicts for sensitivity to imatinib

Published:September 08, 2022DOI:https://doi.org/10.1016/j.cancergen.2022.09.002

      Highlights

      • This literature review has produced the first known, published database of how the primary KIT or PDGFRA variant of a gastrointestinal stromal tumour (GIST) predicts for sensitivity to imatinib.
      • Having excluded wild type GISTs and results for imatinib used as adjuvant therapy, 79 publications (dated August 2001 to March 2022) underwent data extraction.
      • These data showed broad agreement of imatinib sensitivity amongst similar subtypes of KIT or PDGFRA variant.
      • There was also agreement between in vivo versus in vitro/in silico derived sensitivity data for most variants when both data types were available.

      Abstract

      It is well recognized that the primary KIT or PDGFRA variant of a gastrointestinal stromal tumour (GIST) can predict sensitivity to imatinib. However, these data are currently spread across a wide range of publications and have not been collated as one reference. A broad-ranging literature search was therefore performed to assemble such a database which should help optimize imatinib-based management of GIST patients henceforth. Having excluded wild type GISTs and results for imatinib used as adjuvant therapy, 79 publications (dated August 2001 to March 2022) underwent data extraction. These data on imatinib sensitivity were either derived from in vitro studies, predicted by in silico analysis or based on in vivo clinical patient response. Data interpretation carried some caveats: there was a potential for replication of patient-derived data between older and new publications; only predicted protein sequences were presented; the criteria used to record clinical response were not uniform across all publications; and imatinib dosage could vary between different clinical publications. However, these data showed broad agreement of imatinib sensitivity amongst similar subtypes of KIT or PDGFRA variant. There was also agreement between in vivo versus in vitro/in silico derived sensitivity data for most variants when both data types were available.

      Keywords

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