Gastrointestinal stromal tumor ( GIST) is the most common mesenchymal tissue-derived tumor of the gastrointestinal tract, and epidemiology shows its incidence to be between 0.66-2.20/100,000. And the incidence rate in Shanxi Province, China is as high as 4.3 per 1 million. Functional mutations in CKIT and platelet-derived growth factor receptor α (PDGFRA) tyrosine kinase aberrant activation are key factors in the pathogenesis of GIST, and mutations in both are seen in 80-85% and 5-10% of GIST patients, respectively, with CKIT mutations mainly located in exon 11, including deletion mutations (about 66.9%), point mutations (about 21.5%) and duplication mutations (about 8.8%). The PDGFRA mutations were mainly concentrated in exon 18, while insulin-like growth factor receptor (IGFR) overexpression was also found in some wild-type patients and BRAF V600E mutation was detected in about 13% of wild-type GIST patients. Imatinib is the main target drug for GIST, and is a small molecule tyrosine kinase inhibitor (TKI) that targets c-KIT, PDGFRA and bcr-abl, which acts as a pseudosubstrate to compete with ATP for binding to the KIT/PDGFRA receptor tyrosine kinase site, thereby acting as a signal transducer to inhibit kinase activation. As a first-line drug for the treatment of GIST that cannot be resected or has metastasized, imatinib significantly improves the prognosis of GIST with an efficacy rate of 40%-50%, and an increased duration of stable disease (SD) in 20%-30% of patients, with a median progression-free survival time (PFS) of no more than 2 years. The median progression-free survival time (PFS) does not exceed 2 years. However, imatinib resistance is currently the most difficult clinical problem. According to the time of resistance generation, it can be divided into primary resistance and secondary resistance, and also includes the occurrence of resistance caused by signal bypass activation. 1, primary drug resistance refers to the ineffectiveness of treatment, including the disease progression or disease stabilization less than 6 months after the start of treatment, and this part of patients account for 10-14% of the total GIST population. Primary resistance is mainly seen in patients with wild-type or PDGFRA exon 18 D842V mutation. 2. Secondary resistance refers to the reoccurrence of disease progression after 6 months of disease stabilization following effective initial imatinib treatment, which usually occurs 18-24 months after imatinib treatment. Unlike the relatively single mutation site characteristic of primary mutations, secondary mutations often present a polyclonal and diverse mutation pattern. Secondary mutations were mostly seen in patients with original CKIT exon 11 mutations (73%), followed by those with exon 9 mutations (19%). Hou et al. found that the ligand-dependent pathway mediated by stem cell factor SCF is one of the independent pathogenesis of GIST, independent of CKIT autophosphorylation, and that this pathway cannot be inhibited by imatinib, and that the upregulation of SCF expression was detected in patients treated with imatinib, which may be related to the development of secondary resistance to imatinib. This may be related to the development of secondary resistance to imatinib. Tumors grow rapidly after GIST resistance and rarely have the chance to be surgically resected again. Therefore, the selection of targeted drugs and treatment strategies after imatinib resistance is a hot topic of current research. The NCCN guidelines suggest that imatinib may be dosed up to 800 mg/d in the event of disease progression during imatinib treatment, if poor compliance can be excluded from affecting efficacy. Therefore, reintroduction of imatinib is a recommended option for patients who progress after imatinib discontinuation. Second-line use Sunitinib is a small molecule multi-target tyrosine kinase inhibitor that inhibits multiple receptor tyrosine kinases associated with tumor growth and angiogenesis, and was approved by the US FDA in 2006 for second-line use in GIST that is intolerant to imatinib or whose disease progresses after treatment. Studies have concluded that patients with mutations at different exon sites exhibit different sensitivities to sunitinib, with patients with secondary mutations located in exons 13 or 14 showing better efficacy to sunitinib, while mutations located in exon 17 are resistant to sunitinib. Sequential use of imatinib Imatinib continues to be effective in patients who have failed second- or even third-line therapy. the NCCN states that GISTs that present with local progression and fail to benefit from an existing TKI should be treated with an option that was once effective and well-tolerated. This study suggests that TKI-sensitive clones still exist in secondary resistant GISTs, and that continued TKl therapy may delay GIST progression, a sequential treatment approach that may help address tumor heterogeneity. Despite the achievements of GIST-targeted therapies, close to half of imatinib-resistant patients still do not seem to benefit from various second- or third-line treatments. It is indisputable that the role of genetic testing in predicting targeted efficacy, resistance mechanisms and guiding clinical practice in GIST is becoming more and more obvious, and individualized targeted therapy for GIST guided by molecular biology is the future trend. With the development of various new drugs, more attention should be paid to prospective studies of different individualized treatment strategies for different drug resistance mechanisms in the future.