Targeted therapy based treatment of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of gastrointestinal tract. Oncogenic activating mutations

in the receptor tyrosine kinases, KIT (75–80 %) and platelet- derived growth factor receptor alpha (PDGFRA, 10 %) play a crucial

role in the molecular pathogenesis of GIST. Complete surgical resection is the standard treatment for localized GISTs, however, recurrence

is observed in approximately a third of patients 2 years following resection. Better treatment strategies and targeted therapies

have improved survival rates for patients with GIST significantly. Imatinib, the receptor tyrosine kinase inhibitor, has revolutionized the

therapeutic landscape for GIST patients and remains the mainstay first-line clinical option for both unresectable and advanced GISTs,

as well as for adjuvant treatment after resection of high risk GISTs. Sunitinib is indicated as second-line therapy. Regorafenib has been

approved recently as third-line treatment of patients who progressed on or are intolerant to prior imatinib and sunitinib. Early identification

of patients with suboptimal response to therapy and treatment failure, as well as intolerable toxicities, is an important issue of

a multidisciplinary personalized treatment of patients with GIST.

Keywords: gastrointestinal stromal tumors, targeted therapy, imatinib, sunitinib, regorafenib