Integrating analysis of proteome profile and drug screening identifies therapeutic potential of MET pathway for the treatment of malignant peripheral nerve sheath tumor.

IF 3.8 3区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Expert Review of Proteomics Pub Date : 2023-04-01 DOI:10.1080/14789450.2023.2218035

Ryuto Tsuchiya, Yuki Yoshimatsu, Rei Noguchi, Yooksil Sin, Takuya Ono, Taro Akiyama, Hidetaka Kosako, Akihiko Yoshida, Seiji Ohtori, Akira Kawai, Tadashi Kondo

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引用次数: 0

Abstract

Background: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with a poor prognosis that requires novel therapeutic agents. Proteome information is useful for identifying new therapeutic candidates because it directly reflects the biological phenotype. Additionally, in vitro drug screening is an effective tool to identify candidate drugs for common cancers. Hence, we attempted to identify novel therapeutic candidates for MPNST by integrating proteomic analysis and drug screening.

Methods: We performed comprehensive proteomic analysis on 23 MPNST tumor samples using liquid chromatography - tandem mass spectrometry to identify therapeutic targets. We also conducted drug screening of six MPNST cell lines using 214 drugs.

Results: Proteomic analysis revealed that the MET and IGF pathways were significantly enriched in the local recurrence/distant metastasis group of MPNST, whereas drug screening revealed that 24 drugs showed remarkable antitumor effects on the MPNST cell lines. By integrating the results of these two approaches, MET inhibitors, crizotinib and foretinib, were identified as novel therapeutic candidates for the treatment of MPNST.

Conclusions: We successfully identified novel therapeutic candidates for the treatment of MPNST, namely crizotinib and foretinib, which target the MET pathway. We hope that these candidate drugs will contribute to the treatment of MPNST.

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结合蛋白质组谱分析和药物筛选，确定MET通路治疗恶性周围神经鞘肿瘤的治疗潜力。

背景:恶性周围神经鞘肿瘤(MPNST)是一种预后不良的侵袭性肉瘤，需要新的治疗药物。蛋白质组信息对于确定新的治疗候选物是有用的，因为它直接反映了生物学表型。此外，体外药物筛选是确定常见癌症候选药物的有效工具。因此，我们试图通过结合蛋白质组学分析和药物筛选来确定新的MPNST治疗候选药物。方法:采用液相色谱-串联质谱法对23例MPNST肿瘤样本进行全面的蛋白质组学分析，以确定治疗靶点。我们还使用214种药物对6种MPNST细胞系进行了药物筛选。结果:蛋白质组学分析显示，MPNST局部复发/远处转移组MET和IGF通路显著富集，而药物筛选显示24种药物对MPNST细胞系具有显著的抗肿瘤作用。通过整合这两种方法的结果，MET抑制剂克里唑替尼和福替尼被确定为治疗MPNST的新候选药物。结论:我们成功地确定了治疗MPNST的新候选药物，即克唑替尼和福替尼，它们靶向MET途径。我们希望这些候选药物将有助于MPNST的治疗。

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

Expert Review of Proteomics 生物-生化研究方法

CiteScore

7.60

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Expert Review of Proteomics (ISSN 1478-9450) seeks to collect together technologies, methods and discoveries from the field of proteomics to advance scientific understanding of the many varied roles protein expression plays in human health and disease. The journal coverage includes, but is not limited to, overviews of specific technological advances in the development of protein arrays, interaction maps, data archives and biological assays, performance of new technologies and prospects for future drug discovery. The journal adopts the unique Expert Review article format, offering a complete overview of current thinking in a key technology area, research or clinical practice, augmented by the following sections: Expert Opinion - a personal view on the most effective or promising strategies and a clear perspective of future prospects within a realistic timescale Article highlights - an executive summary cutting to the author''s most critical points.