A new strategy targeting NTRK in the treatment of recurrent and refractory solid tumors

doi:10.3760/cma.j.cn371439-20200212-00049

Abstract

Abstract:

NTRK gene fusions are oncogenic drivers of various paediatric and adult tumor types. The fusion proteins encoded by these fusion genes have tropomyosin related kinase (TRK) tyrosine kinase domains, which provides novel targets for tumor targeted therapy. The treatment of patients with NTRK fusion-positive cancers with a first-generation TRK inhibitor, such as larotrectinib or entrectinib, is associated with high response rate (>75%), regardless of tumor histology. The first-generation TRK inhibitors are well tolerated by most patients. Chronic use of TRK inhibitors can lead to secondary resistance, and the resistance is mediated by the acquisition of NTRK kinase domain mutations. Fortunately, certain resistance mutations can be overcome by second-generation TRK inhibitors, including LOXO-195 and TPX-0005 that are being explored in clinical trials. As for its good efficacy and safety, NTRK targeted therapy is a new choice for the treatment of relapsed refractory solid tumors with NTRK fusion.

Key words: Gene fusion, Molecular targeted therapy, Larotrectinib, Entrectinib

Hao Xueyan, Liu Fengling. A new strategy targeting NTRK in the treatment of recurrent and refractory solid tumors[J]. Journal of International Oncology, 2020, 47(7): 423-427.

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