Title : Acquired resistance to FGFR inhibitor in diffuse-type gastric cancer through an AKT-independent PKC-mediated phosphorylation of GSK 3 β

Page 1 of 25 Title: Acquired resistance to FGFR inhibitor in diffuse-type gastric cancer through an AKTindependent PKC-mediated phosphorylation of GSK3β Authors: Wen Min Lau1, Eileen Teng1, Kie Kyon Huang1,2, Jin Wei Tan1, Kakoli Das2, Zhijiang Zang2, Tania Chia1, Ming Teh3, Koji Kono1,4, Wei Peng Yong1,5, Asim Shabbir4, Amy Tay4, Niam Sin Phua4, Patrick Tan1,2,*, Shing Leng Chan1,*, Jimmy Bok Yan So4. Affiliations: 1Cancer Science Institute of Singapore, National University of Singapore 2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 3Department of Pathology, National University of Singapore 4Department of Surgery, National University of Singapore, National University Hospital 5Department of Haematology-Oncology, National Cancer Institute of Singapore, National University Hospital, Singapore,

[1]  J. Datta,et al.  Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398 , 2017, Molecular Cancer Therapeutics.

[2]  Gad Getz,et al.  Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma. , 2017, Cancer discovery.

[3]  S. Park,et al.  Acquired resistance to LY2874455 in FGFR2-amplified gastric cancer through an emergence of novel FGFR2-ACSL5 fusion , 2017, Oncotarget.

[4]  Manuel Hidalgo,et al.  Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  K. Kojima,et al.  Different clinical significance of FGFR1–4 expression between diffuse-type and intestinal-type gastric cancer , 2017, World Journal of Surgical Oncology.

[6]  B. Cho,et al.  Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy , 2016, Oncogenesis.

[7]  Jian Ning,et al.  Molecular determinants of sensitivity and resistance to FGFR inhibition in FGFR2-amplified gastric cancer , 2016 .

[8]  Sue Chua,et al.  High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial. , 2016, Cancer discovery.

[9]  Yoon Young Choi,et al.  Establishment and characterisation of patient-derived xenografts as paraclinical models for gastric cancer , 2016, Scientific Reports.

[10]  Wenting Xu,et al.  Molecular targeted therapy for the treatment of gastric cancer , 2016, Journal of Experimental & Clinical Cancer Research.

[11]  Y. Ishikawa,et al.  Prognostic impact of KRAS mutant type and MET amplification in metastatic and recurrent gastric cancer patients treated with first-line S-1 plus cisplatin chemotherapy , 2016, Genes & cancer.

[12]  Meizhuo Zhang,et al.  Patient-Derived Gastric Carcinoma Xenograft Mouse Models Faithfully Represent Human Tumor Molecular Diversity , 2015, PloS one.

[13]  R. Jope,et al.  Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. , 2015, Pharmacology & therapeutics.

[14]  P. Coveney,et al.  The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study , 2015, EBioMedicine.

[15]  Zhe Zhang,et al.  Multiple receptor tyrosine kinase activation attenuates therapeutic efficacy of the fibroblast growth factor receptor 2 inhibitor AZD4547 in FGFR2 amplified gastric cancer , 2014, Oncotarget.

[16]  Rachel G Liao,et al.  Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors , 2014, Proceedings of the National Academy of Sciences.

[17]  René Bernards,et al.  Feedback and redundancy in receptor tyrosine kinase signaling: relevance to cancer therapies. , 2014, Trends in biochemical sciences.

[18]  Wenping Ding,et al.  Clinical response to sunitinib as a multitargeted tyrosine-kinase inhibitor (TKI) in solid cancers: a review of clinical trials , 2014, OncoTargets and therapy.

[19]  M. Salto‐Tellez,et al.  CD44v8-10 is a cancer-specific marker for gastric cancer stem cells. , 2014, Cancer research.

[20]  H. Grabsch,et al.  FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study , 2014, British Journal of Cancer.

[21]  S. Cook,et al.  Tumour cell responses to new fibroblast growth factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation in FGFR3 as a mechanism of acquired resistance , 2013, Oncogene.

[22]  J. Ji,et al.  FGFR2 Gene Amplification in Gastric Cancer Predicts Sensitivity to the Selective FGFR Inhibitor AZD4547 , 2013, Clinical Cancer Research.

[23]  Fabrice Andre,et al.  Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives. , 2013, Cancer discovery.

[24]  David M. Thomas,et al.  FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. , 2012, Cancer discovery.

[25]  Andrew P Thomas,et al.  AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. , 2012, Cancer research.

[26]  Levi A Garraway,et al.  Circumventing cancer drug resistance in the era of personalized medicine. , 2012, Cancer discovery.

[27]  Christopher A. Miller,et al.  VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. , 2012, Genome research.

[28]  H. Hass,et al.  Signet Ring Cell Carcinoma of the Stomach Is Significantly Associated with Poor Prognosis and Diffuse Gastric Cancer (Lauren’s): Single-Center Experience of 160 Cases , 2011, Oncology Research and Treatment.

[29]  W. Knoefel,et al.  Prognostic factors in patients with diffuse type gastric cancer (linitis plastica) after operative treatment , 2011, European journal of medical research.

[30]  N. Turner,et al.  Fibroblast growth factor signalling: from development to cancer , 2010, Nature Reviews Cancer.

[31]  T. Chou.  Drug combination studies and their synergy quantification using the Chou-Talalay method. , 2010, Cancer research.

[32]  Hua Yu,et al.  Sunitinib Induces Apoptosis and Growth Arrest of Medulloblastoma Tumor Cells by Inhibiting STAT3 and AKT Signaling Pathways , 2010, Molecular Cancer Research.

[33]  C. V. D. Velde,et al.  Gastric cancer , 2009, The Lancet.

[34]  S. Choi,et al.  Advanced Gastric Carcinoma with Signet Ring Cell Histology , 2007, Oncology.

[35]  L. Chow,et al.  Sunitinib: from rational design to clinical efficacy. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  M Vasei,et al.  Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers , 2006, British Journal of Cancer.

[37]  T. Kim,et al.  Scirrhous gastric carcinoma: endoscopy versus upper gastrointestinal radiography. , 2004, Radiology.

[38]  P. Campochiaro,et al.  PKC412--a protein kinase inhibitor with a broad therapeutic potential. , 2000, Anti-cancer drug design.

[39]  T. Saito,et al.  Borrmann's type IV gastric cancer: clinicopathologic analysis. , 1999, Canadian journal of surgery. Journal canadien de chirurgie.

[40]  J. Ware,et al.  The structure and biological activities of the widely used protein kinase inhibitor, H7, differ depending on the commercial source. , 1992, Biochemical and biophysical research communications.

[41]  J. Woodgett,et al.  Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes. , 1992, The Journal of biological chemistry.

[42]  G. Aranha,et al.  Gastric linitis plastica is not a surgical disease. , 1989, Surgery.

[43]  P. Laurén,et al.  THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. , 1965, Acta pathologica et microbiologica Scandinavica.

[44]  S. Ahrendt,et al.  Aggressive Locoregional Surgical Therapy for Gastric Peritoneal Carcinomatosis , 2013, Annals of Surgical Oncology.

[45]  L. Meijer,et al.  1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. , 2004, Bioorganic & medicinal chemistry letters.

[46]  W. Hyung,et al.  Early gastric carcinoma with signet ring cell histology , 2002, Cancer.