Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK -Rearranged NSCLC

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Ka-Won NohYoon-La Choi

Abstract

Purpose: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small-molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication.Experimental Design: We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization and then conducted multiplex gene expression analysis. We also performed a clinicopathologic analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and in vivo lung cancer model studies were performed.Results: Among patients with ALK-rearranged NSCLC, integrin β3 (ITGB3) was one of the overexpressed genes in comparison with that in ALK-negative NSCLC (P = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages (P < 0.005; P < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led ...Continue Reading

References

Oct 4, 2003·Science·Seiji TadokoroDavid A Calderwood
Dec 25, 2004·Biostatistics·Sin-Ho JungStanley Young
Sep 29, 2005·Statistics in Medicine·Sin-Ho JungStephen L George
Mar 31, 2007·Nature Methods·Genee Y LeeMina J Bissell
May 16, 2009·Science·Markus MoserReinhard Fässler
Dec 24, 2009·Nature Reviews. Cancer·Jay S Desgrosellier, David A Cheresh
Feb 9, 2010·Cell Adhesion & Migration·Francesca CaccavariGuido Serini
Apr 15, 2010·Cancer Research·Barbara Garmy-SusiniJudith A Varner
Jan 5, 2011·Experimental & Molecular Medicine·Kyoungsook ParkJe-Ho Lee
Dec 2, 2011·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jin Ho PaikJin-Haeng Chung
Jan 12, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert C DoebeleD Ross Camidge
Jan 27, 2012·Science Translational Medicine·Ryohei KatayamaJeffrey A Engelman
Apr 5, 2012·Nature Reviews. Clinical Oncology·D Ross Camidge, Robert C Doebele
Jun 4, 2013·The New England Journal of Medicine·Alice T ShawPasi A Jänne
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mark W RichardsRichard Bayliss
Apr 22, 2014·Nature Cell Biology·Laetitia SeguinDavid A Cheresh
Aug 1, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Sep 1, 2014·Nature Medicine·Christine M LovlyWilliam Pao
Feb 27, 2015·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Ryong Nam KimJhingook Kim
Jun 23, 2015·Journal of Pathology and Translational Medicine·In Ho ChoiJoungho Han
Oct 6, 2015·Oncotarget·Doo-Yi OhSangyong Song
Jan 12, 2016·Therapeutic Advances in Medical Oncology·Ivana Sullivan, David Planchard
Jan 30, 2016·Nature Reviews. Drug Discovery·Klaus LeySanford Shattil
Feb 27, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Lu ChenW Douglas Cress
Jan 27, 2017·Cancer Discovery·Jessica J LinAlice T Shaw
Sep 13, 2017·Cancer Discovery·Laetitia SeguinDavid A Cheresh
Oct 27, 2017·Nature Reviews. Cancer·Julia Rotow, Trever G Bivona

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