Abstract
Gastrointestinal stromal tumors (GISTs) originate from interstitial cells of Cajal and account for over 5,000 newly diagnosed cases in the United States. The discovery of activated KIT and PDGFRA mutations and introduction of imatinib revolutionized the treatment strategy and opened up the new era of target therapy for solid tumors. Although surgery remains the primary modality of treatment for curative purpose, almost half of the patients experienced disease recurrence. Tailoring (neo)-adjuvant treatment with imatinib is ongoing to meet the need for an effective therapy. Currently, two drugs (sunitinib and regorafenib) have obtained Food and Drug Administration approval for GISTs after imatinib failure. However, most of the patients eventually progress due to primary or secondary resistance. Deeper understanding of the molecular mechanisms will guide us to develop personalized strategies in the future. Discussion in this review includes current standard management and the most recent advances and multiple ongoing clinical trials with different approaches. This review will provide further steps to be taken to conquer refractory disease.
Highlights
Gastrointestinal stromal tumors (GISTs) are known as the most common mesenchymal tumor of gastrointestinal (GI) system in the United States [1] with the incidence of 10–15 cases per million [2]
The homologous structure between KIT, PDGFRA, and ABL kinases facilitated the introduction of imatinib to the therapy of GISTs in 2000 [10, 11] and the Food and Drug Administration (FDA) granted the approval
Of the 341 patients from SSG XVIII/AIO trial, the study again found that KIT exon 11 deletion or insertion-deletion mutations involved codons 557 and/or 558 had better recurrence free survival (RFS) following 3 years adjuvant imatinib treatment compared with 1 year, but not there was not a statistical difference in the in exon 11 substitution mutations, exon 9 mutations, PDGFRA mutation, or WT-GISTs; there were too few cases with other mutations to make conclusions [40]
Summary
Gastrointestinal stromal tumors (GISTs) originate from interstitial cells of Cajal and account for over 5,000 newly diagnosed cases in the United States. The discovery of activated KIT and PDGFRA mutations and introduction of imatinib revolutionized the treatment strategy and opened up the new era of target therapy for solid tumors. Surgery remains the primary modality of treatment for curative purpose, almost half of the patients experienced disease recurrence. Tailoring (neo)-adjuvant treatment with imatinib is ongoing to meet the need for an effective therapy. Two drugs (sunitinib and regorafenib) have obtained Food and Drug Administration approval for GISTs after imatinib failure. Most of the patients eventually progress due to primary or secondary resistance. Discussion in this review includes current standard management and the most recent advances and multiple ongoing clinical trials with different approaches. This review will provide further steps to be taken to conquer refractory disease
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