Larotrectinib
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Larotrectinib is a kinase inhibitor used to treat solid tumors with neurotrophic receptor tyrosine kinase gene fusion, are metastatic, high risk for surgery, or have no alternative treatments.
Larotrectinib is a kinase inhibitor used to treat solid tumors with neurotrophic receptor tyrosine kinase gene fusion, are metastatic, high risk for surgery, or have no alternative treatments.
Tropomysoin Receptor Kinases (TRK) like TRKA, TRKB, and TRKC elicit activities that regulate the natural growth, differentiation, and survival of neurons when they interact with endogenous neutrotrophin ligands . TRKA, TRKB, and TRKC are themselves encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively . It has been discovered that chromosomal rearrangements involving in-frame fusions of these genes with various partners, translocations in the TRK kinase domains, mutations in the TRK ligand-binding site, amplifications of NTRK, or the expression of TRK splice variants can result in constitutively-activated chimeric TRK fusion proteins that can act as oncogenic drivers that promote cell proliferation and survival in tumor cell lines . Subsequently, larotrectinib functions as an inhibitor of TRKs including TRKA, B, and C . In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression . Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R . Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L .
用于治疗携带NTRK基因融合的局部晚期或转移性实体瘤的成人和儿童患者。包括肺癌、甲状腺癌、黑色素瘤、胃肠癌、结肠癌、软酿肉瘤、唾液腺、婴儿纤维肉瘤、阑尾癌、乳腺癌、胆管癌、胰腺癌等多种疾病。
