MET kinase inhibitor SGX523 synergizes with epidermal growth factor receptor inhibitor erlotinib in a hepatocyte growth factor-dependent fashion to suppress carcinoma growth

Cancer Research
Yu-Wen ZhangGeorge F Vande Woude

Abstract

The hepatocyte growth factor (HGF)-MET pathway supports several hallmark cancer traits, and it is frequently activated in a broad spectrum of human cancers (http://www.vai.org/met/). With the development of many cancer drugs targeting this pathway, there is a need for relevant in vivo model systems for preclinical evaluation of drug efficacy. Here, we show that production of the human HGF ligand in transgenic severe combined immunodeficient mice (hHGF(tg)-SCID mice) enhances the growth of many MET-expressing human carcinoma xenografts, including those derived from lung, breast, kidney, colon, stomach, and pancreas. In this model, the MET-specific small-molecule kinase inhibitor SGX523 partially inhibits the HGF-dependent growth of lung, breast, and pancreatic tumors. However, much greater growth suppression is achieved by combinatorial inhibition with the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. Together, these results validate the hHGF(tg)-SCID mouse model for in vivo determination of MET sensitivity to drug inhibition. Our findings also indicate that simultaneously targeting the MET and EGFR pathways can provide synergistic inhibitory effects for the treatment of cancers in which both pathways are a...Continue Reading

References

Nov 1, 1992·Molecular and Cellular Biology·S RongG F Vande Woude
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
May 11, 2002·Nature Reviews. Cancer·Livio Trusolino, Paolo M Comoglio
Jul 30, 2003·Cancer Metastasis Reviews·Patrick C MaRavi Salgia
Dec 20, 2003·Nature Reviews. Molecular Cell Biology·Carmen BirchmeierGeorge F Vande Woude
Jul 21, 2004·Cancer Cell·Yu-Wen ZhangGeorge F Vande Woude
Jan 7, 2006·Cancer Research·Monica Kong-BeltranRobert Yauch
Aug 25, 2006·Nature Reviews. Cancer·Kohzoh Imai, Akinori Takaoka
Dec 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·James BeanWilliam Pao
Apr 15, 2008·Current Opinion in Genetics & Development·Beatrice S Knudsen, George Vande Woude
May 31, 2008·Nature Reviews. Drug Discovery·Paolo M ComoglioLivio Trusolino
Dec 25, 2008·Neoplasia : an International Journal for Oncology Research·Brian B HainesWeisheng Zhang
Mar 26, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Joseph Paul EderPatricia M LoRusso
Feb 5, 2010·Cancer Cell·Alexa B TurkePasi A Jänne

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Citations

Jan 8, 2013·Current Oncology Reports·Ulka Vaishampayan
Jun 19, 2013·Current Oncology Reports·Shirish M Gadgeel
Jan 25, 2012·Nature Reviews. Cancer·Ermanno GherardiGeorge Vande Woude
Dec 7, 2011·Nature Reviews. Gastroenterology & Hepatology·Alphonse E Sirica
Dec 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Qian XieGeorge F Vande Woude
Jun 16, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·T MimaeH Tsuda
May 31, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hai XuJill M Siegfried
Sep 10, 2011·Therapeutic Advances in Medical Oncology·Martin SattlerRavi Salgia
Jun 5, 2013·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Vladimira KoudelakovaMarian Hajduch
Dec 1, 2015·Expert Review of Anticancer Therapy·Nabin Khanal, Apar Kishor Ganti
May 24, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Vikas BhardwajJames Welsh
Jun 19, 2012·Seminars in Cancer Biology·Chuan Shen, William G Kaelin
Jul 19, 2011·Hematology/oncology Clinics of North America·Lianjie Li, William G Kaelin
Feb 1, 2011·Drug Discoveries & Therapeutics·J J GaoW Tang
Apr 25, 2015·The Journal of Investigative Dermatology·Soonyean HwangByungwoo Ryu
Mar 13, 2014·International Journal of Cancer. Journal International Du Cancer·Yu Jin KimYoon-La Choi
Apr 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Geoffrey Wayne KrampitzIrving L Weissman
Sep 19, 2015·Journal of Translational Medicine·Jennifer JohnsonQian Xie
Oct 22, 2010·Cell Cycle·James D Webb, M Celeste Simon
Jun 23, 2016·Science Signaling·Christophe CataissonStuart H Yuspa
Sep 13, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Shiyong LiMao Mao
Oct 9, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Eric B Haura, Matthew A Smith
Feb 6, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·Heekyoung YangDo-Hyun Nam
Apr 17, 2012·Expert Review of Anticancer Therapy·Astrid BelalcazarEdgardo S Santos
Jan 15, 2015·Biomedicines·Giuditta Viticchiè, Patricia A J Muller
Mar 20, 2019·Journal of Experimental & Clinical Cancer Research : CR·Teng LuoChang-Yan Li
Sep 24, 2020·Journal of Experimental & Clinical Cancer Research : CR·Hang-Ping YaoMing-Hai Wang
Oct 4, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mansoureh SameniBonnie F Sloane
Aug 3, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lars D EngstromJames G Christensen

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