PTPN9 regulates HER3 phosphorylation during trastuzumab treatment and loss of PTPN9 is a potential biomarker for trastuzumab resistance in HER2 positive breast cancer  

作　　者：Abul Azad Maryam Arshad Daniele Generali Katharina Feldinger Merel Gijsen Carla Strina Mariarosa Cappelletti Daniele Andreis Russell Leek Syed Haider Pirkko-Liisa Kellokumpu-Lehtinen Ioannis Roxanis Adrian Llewellyn Harris Abeer Mahmoud Shaaban Heikki Joensuu Anthony Kong 

机构地区：[1]Department of Oncology,The Weatherall Institute of Molecular Medicine,University of Oxford,Oxford,UK [2]Institute of Genomic and Cancer Sciences,Vincent Drive,University of Birmingham,Birmingham,UK [3]Comprehensive Cancer Centre,Kings’College London,London,UK [4]U.O.Multidisciplinare di Patologia Mammaria,U.S Terapia Molecolare e Farmacogenomica,A.O.Instituti Ospitalieri di Cremona,Viale Concordia 1,Cremona,Italy [5]Biostatistics and Clinical Trials Unit,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS,Forlì-Cesena,Meldola,Italy [6]The Institute of Cancer Research,London,UK [7]Department of Oncology,Tampere University Hospital and Tampere University,Tampere,Finland [8]Department of Cellular Pathology,Oxford University Hospitals and Oxford Biomedical Research Centre,Oxford,UK [9]Department of histopathology,Queen Elizabeth Hospital Birmingham,Birmingham,UK [10]Department of Oncology,Helsinki University Hospital and University of Helsinki,Helsinki,Finland

出　　处：《Cancer Communications》2025年第1期68-73,共6页癌症通讯(英文)

基　　金：supported by Breakthrough Breast cancer(Grant number:CSFKong)through Holbeck Charitable Trust;Prof A Shaaban is supported by Birmingham CRUK Centre grant.

摘　　要：Although trastuzumab does not bind to human epidermal growth factor receptor 3(HER3),it dephosphorylates HER3 through a previously unknownmechanism.In addition,HER3 is reactivated during prolonged trastuzumab treatment and upon resistance[1].Previous study showed that tyrosine-protein phosphatase non-receptor type 9(PTPN9)inhibits STAT3/STAT5 signalling by dephosphorylation of epidermal growth factor receptor(EGFR)and human epidermal growth factor receptor 2(HER2)in breast cancer[2],but how this would affect HER3 was not analyzed especially in relation to trastuzumab treatment.We investigated the role of PTPN9 in HER3 signaling in relation to trastuzumab treatment and resistance in HER2 positive breast cancer.The materials and methods applied in this research were described in the supplementary materials.

关 键 词：HER3 TRASTUZUMAB TREATMENT HER2 PTP 

分 类 号：R73[医药卫生—肿瘤]