Abstract
The approval of imatinib for the treatment of patients with gastrointestinal stromal tumor has (GIST) revolutionized the treatment in the adjuvant setting and metastatic disease. Imatinib is an inhibitor of the receptor tyrosine kinases KIT and platelet-derived growth factor receptor (PDGFR), which are constitutively activated in most cases of GIST. Even though substantial survival improvements have been observed with imatinib, primary or secondary resistance to imatinib represents a major challenge in the treatment of GIST. This short review focusses on treatment strategies to overcome resistance and provides an overview of promising new agents currently evaluated for imatinib-refractory disease.
Highlights
Gastrointestinal stromal tumors (GIST) are a distinct subgroup of mesenchymal neoplasms
It was only a matter of time before it was noticed that abl, KIT, and platelet-derived growth factor receptor-alpha (PDGFRα) show a similar chemical structure and provide a biologic rationale to evaluate imatinib in patients with GIST [10]
The advances in oncologic research and the understanding of fundamental molecular cancer pathways have led to highly effective targeted treatments in patients with GIST in the past 10 years
Summary
Received: 8 January 2019 / Accepted: 26 March 2019 / Published online: 18 April 2019. Summary The approval of imatinib for the treatment of patients with gastrointestinal stromal tumor has (GIST) revolutionized the treatment in the adjuvant setting and metastatic disease. Imatinib is an inhibitor of the receptor tyrosine kinases KIT and platelet-derived growth factor receptor (PDGFR), which are constitutively activated in most cases of GIST. Even though substantial survival improvements have been observed with imatinib, primary or secondary resistance to imatinib represents a major challenge in the treatment of GIST. This short review focusses on treatment strategies to overcome resistance and provides an overview of promising new agents currently evaluated for imatinib-refractory disease
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