TRKing down drug resistance in NTRK fusion-positive cancers†

IF 5.6 2区医学 Q1 ONCOLOGY

The Journal of Pathology Pub Date : 2024-07-29 DOI:10.1002/path.6341

Abigail G Parrish, Frank Szulzewsky

引用次数: 0

Abstract

In a recent issue of The Journal of Pathology, Chen and colleagues established novel patient-derived ex vivo models of NTRK fusion-positive soft tissue sarcoma to characterize resistance mechanisms against targeted therapy with tyrosine kinase inhibitors. Prolonged exposure to escalating concentrations of the tyrosine kinase inhibitor, entrectinib, ultimately led to the occurrence of resistant clones that harbored an inactivating mutation in the NF2 gene, not previously described in this context, accompanied by increased PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling. Finally, an inhibitor screen identified, among others, MEK and mTOR inhibitors as potential combination agents. © 2024 The Pathological Society of Great Britain and Ireland.

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通过 TRK 降低 NTRK 融合阳性癌症的耐药性†。

在最近一期《病理学杂志》（The Journal of Pathology）上，Chen及其同事建立了新型NTRK融合阳性软组织肉瘤患者衍生体外模型，以研究酪氨酸激酶抑制剂靶向治疗的耐药机制。长期暴露于浓度不断升高的酪氨酸激酶抑制剂entrectinib，最终导致了耐药克隆的出现，这种耐药克隆在NF2基因中携带一种失活突变，而这种突变以前从未在这种情况下被描述过，同时伴随着PI3K/AKT/mTOR和Ras/Raf/MEK/ERK信号的增强。最后，通过抑制剂筛选发现，MEK 和 mTOR 抑制剂是潜在的联合用药。© 2024 大不列颠及爱尔兰病理学会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

The Journal of Pathology 医学-病理学

CiteScore

14.10

自引率

1.40%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.