Abstract
Gastrointestinal stromal tumors (GISTs) are the most common types of malignant mesenchymal tumors in the gastrointestinal tract, with an estimated incidence of 1.5/100.000 per year and 1–2% of gastrointestinal neoplasms. About 75–80% of patients have mutations in the KIT gene in exons 9, 11, 13, 14, 17, and 5–10% of patients have mutations in the platelet-derived growth factor receptor a (PDGFRA) gene in exons 12, 14, 18. Moreover, 10–15% of patients have no mutations and are classified as wild type GIST. The treatment for metastatic or unresectable GISTs includes imatinib, sunitinib, and regorafenib. So far, GIST therapies have raised great expectations and offered patients a better quality of life, but increased pharmacological resistance to tyrosine kinase inhibitors is often observed. New treatment options have emerged, with ripretinib, avapritinib, and cabozantinib getting approvals for these tumors. Nowadays, immune checkpoint inhibitors form a new landscape in cancer therapeutics and have already shown remarkable responses in various tumors. Studies in melanoma, non-small-cell lung cancer, and renal cell carcinoma are very encouraging as these inhibitors have increased survival rates. The purpose of this review is to present alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors).
Highlights
Gastrointestinal Stromal Tumors (GISTs) are the most common types of mesenchymal tumors of the gastrointestinal tract and originate from interstitial Cajal cells [1]
Recent studies have shown that ligands from the fibroblast growth factors (FGF) family reduce imatinib’s effect on GIST cells, and
Nagata et al showed that c-KIT and Epidermal growth factor receptor (EGFR) phosphorylation status is similar in imatinib-resistant GIST cell lines
Summary
Gastrointestinal Stromal Tumors (GISTs) are the most common types of mesenchymal tumors of the gastrointestinal tract and originate from interstitial Cajal cells [1]. Mutations in the PDGFRA gene are identified in exons 12, 14, 18 to 5–10% of patients. 10–15% of patients have no mutations and are classified as wild type GIST [6,7]. Molecular characterization of GISTs has revealed novel mutations to BRAF, neurofibromatosis type 1 (NF1), and succinate dehydrogenase (SDH) in small percentages [8]. Even after comprehensive analysis, a group of GISTs with no mutations is identified [9]. For metastatic or recurrent GIST, the first treatment line is the tyrosine kinase inhibitor, imatinib mesylate (IM). Patients with PDGFRA exon 18 mutation must receive avapritinib on the first line (Table 1). Pediatric GISTs represent a clinically and molecularly distinct subset, characterized by the absence of c-KIT/PDGFRA mutations. Syndromes linked to GISTs are the Carney triad syndrome, Carney-Stratakis syndrome, and Neurofibromatosis type I [22]
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