Current clinical strategy for imatinib-resistant gastrointestinal stromal tumors

Before the advent of imatinib, no effective agent was available for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GISTs). However, the treatment strategy changed and the prognosis of patients with advanced or recurrent GIST improved remarkably after the development of imatinib. Despite the high rate of clinical benefit of imatinib in GIST patients, more than half of GIST patients eventually develop primary or secondary resistance to imatinib, resulting in the progression of the disease. It has also been reported that about 5% of patients are intolerant to imatinib. An effective treatment strategy for imatinib-resistant GIST is needed. The National Comprehensive Cancer Network guidelines recommend a multidisciplinary approach, but the therapeutic modalities are still limited, and none are able to achieve complete remission. In this review, we summarize the current understandings of the mechanism of imatinib resistance and the clinical strategies used against imatinib-resistant GIST, including surgical intervention, escalation of imatinib dose, and use of sunitinib or other agents. Understanding these issues may help in the development of a new treatment paradigm for GIST patients.