Abstract: Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. Tyrosine kinase inhibitors (TKIs) as targeted agents are the backbone for advanced GIST treatment. During the past years, with the unceasing emergence of new TKIs (such as ripretinib and avapritinib), the treatment paradigm of advanced GIST has dramatically changed, which also have significantly improved the survival and quality of life for patients with GIST. The discoveries of KIT/PDGFRA and other genetic pathways have led to the deeper understanding of mechanisms of TKIs and the innovations of targeted agents. The research and development of novel targets and drugs, such as PDGFRA receptor antagonists (biologics), MEK inhibitors, TRK inhibitors, CDK inhibitors and immune checkpoint inhibitors, has provided more treatment options for advanced GIST. Strategies of targeted therapy for advanced GIST will be continuously optimized. This article reviewed the recent advances and future direction of drug therapy for advanced GIST.

Key words: Advanced gastrointestinal stromal tumor, Tyrosine kinase inhibitor, Drug resistance, Advances