Tumor-Intrinsic Kinome Landscape of Pancreatic Cancer Reveals New Therapeutic Approaches.

IF 29.7 1区 医学 Q1 ONCOLOGY Cancer discovery Pub Date : 2025-02-07 DOI:10.1158/2159-8290.CD-23-1480
Yi Xu, Xianlu L Peng, Michael P East, Ian C McCabe, Grace C Stroman, Madison R Jenner, Priscilla S Chan, Ashley B Morrison, Emily C Shen, Silvia G Hererra, Chinmaya U Joisa, Naim U Rashid, Alina C Iuga, Shawn M Gomez, Lisa Miller-Phillips, Stefan Boeck, Volker Heinemann, Michael Haas, Steffen Ormanns, Gary L Johnson, Jen Jen Yeh
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Abstract

Significance: We provide a comprehensive tumor-intrinsic kinome landscape that provides a roadmap for the use of kinase inhibitors in PDAC treatment approaches.

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胰腺癌的肿瘤-内在基因图谱揭示了新的治疗方法。
胰腺导管腺癌(PDAC)的有效治疗在很大程度上是难以捉摸的。在这里,我们对102例来自14种独特原发PDAC的患者异种移植物进行了多重激酶抑制剂珠质谱分析,以确定肿瘤内在的kinome景观。我们的发现揭示了三个基因组亚组组成了两个肿瘤内在的基因组亚型,我们称之为kinotypes。kinotypes显示不同激酶类的富集,并概括了先前描述的分子亚型,基底样和经典。基底样肿瘤的基因型表现为受体酪氨酸激酶的富集,而典型肿瘤的基因型则表现为参与Wnt信号和免疫途径的激酶的富集。我们在两项临床试验中验证了我们的发现,并表明只有基底样肿瘤患者从EGFR抑制剂中获得显着益处。我们的研究结果为PDAC提供了一个全面的肿瘤-内在激酶图景,有力地支持可操作的激酶类型特异性靶点,并为PDAC的激酶抑制剂治疗提供了路线图。
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来源期刊
Cancer discovery
Cancer discovery ONCOLOGY-
CiteScore
22.90
自引率
1.40%
发文量
838
审稿时长
6-12 weeks
期刊介绍: Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.
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