Treatments for gastrointestinal stromal tumors that are resistant to standard therapies

The advent of the tyrosine kinase inhibitors imatinib and sunitinib dramatically revolutionized the therapeutic approach to gastrointestinal stromal tumor (GIST) and improved the outcomes of patients who were affected by this rare tumor, becoming the standard first- and second-line systemic therapies for advanced/metastatic GIST. Most patients obtain good, durable responses to treatment; nevertheless, almost all patients develop acquired resistance, which is commonly related to secondary mutations in receptors. Resistance represents an important clinical problem in oncology, underlining the need to identify novel agents in order to overcome it. In this article, we focus on the most recent developments in the therapy of advanced GIST that is resistant to standard therapies, including both new single drugs or drug-drug combinations, and the integration of systemic and locoregional treatment.