Gastrointestinal stromal tumors (GIST) are rare neoplasms arising from the 
interstitial cell of Cajal in the gastrointestinal tract. Two thirds of GIST in 
adult patients have c-Kit mutation and smaller fractions have platelet derived 
growth factor receptor alpha (PDGFRA) mutation. Surgery is the only curative 
treatment for localized disease. Imatinib improves survival when used adjuvantly 
and in advanced disease. Several targeted therapies have also improved survival 
in GIST patients after progression on imatinib including sunitinib and 
regorafenib. Recently, United States Federal and Drug Administration (FDA) 
approved two new tyrosine kinase inhibitors for the treatment of heavily 
pretreated advanced/unresectable GIST including avapritinib (a selective 
inhibitor for PDGFRA exon 18 mutation including D842V mutations) and ripretinib 
(a broad-spectrum kinase inhibitor of c-Kit and PDGFRA). In this article, we 
will provide a comprehensive review of GIST including the current standard of 
care treatment and exploring future paradigm shifts in therapy.