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Imatinib has demonstrated efficacy as a first\u2010line treatment for intermediate\u2010 and high\u2010risk localized GISTs, as well as for relapsed or metastatic progressive GISTs. However, some patients develop resistance to imatinib, which leads to accelerated progression, complex genetic mutations, and high spatiotemporal heterogeneity. The efficacy of the second\u2010, third\u2010, and fourth\u2010line standard treatments recommended by the latest National Comprehensive Cancer Network guidelines is limited, and no unified treatment protocol after the failure of fourth\u2010line therapy exists. Therefore, exploring new treatment modalities is crucial. This article reviews recent research on treatment strategies after the failure of standard treatments for progressive GISTs, including the alternating or combined use of different TKIs, radiotherapy, and immunotherapy. 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