Molecular Pathways: Anticancer Activity by Inhibition of Nucleocytoplasmic Shuttling

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Fabio ConfortiGiuseppe Giaccone

Abstract

A dynamic distribution between nucleus and cytoplasm (nucleocytoplasmic shuttling) is one of the control mechanisms adapted by normal cells to regulate the activity of a variety of molecules. Growing evidence suggests that dysregulation of the nucleocytoplasmic shuttling is involved in promoting abnormal cell survival, tumor progression, and drug resistance, and is associated with poor cancer prognosis. Aberrant nucleocytoplasmic shuttling in cancer cells may result from a hyperactive status of diverse signal-transduction pathways, such as the PI3K-AKT and MAPK pathways, or from alterations in the general nuclear import/export machinery. Among the large number of molecules involved in the shuttling process, exportin XPO1, also known as chromosome region maintenance 1, appears to play a particularly prominent role in pathogenesis of both hematological malignancies and solid tumors. Given the importance of nucleocytoplasmic shuttling in cancer pathogenesis and the rapidly expanding knowledge in this field, attempts have been made to develop compounds able to revert the aberrant nucleocytoplasmic shuttling. A promising new drug, KPT-330 (Selinexor), which belongs to the class of XPO1 inhibitors called selective inhibitors of nucle...Continue Reading

References

Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·U M MollA J Levine
Mar 1, 1996·Molecular and Cellular Biology·U M MollG Zambetti
May 1, 1996·Gynecologic Oncology·I B RunnebaumR Kreienberg
Aug 1, 1996·British Journal of Cancer·E S NewlandsM H Brampton
Oct 23, 1997·Journal of the National Cancer Institute·C L SchlampR W Nickells
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·N KudoS Horinouchi
Dec 28, 1999·Annual Review of Cell and Developmental Biology·D Görlich, U Kutay
Feb 28, 2002·The Journal of Cell Biology·Anne BrunetMichael B Yaffe
Jan 16, 2003·Cell·Anatoly Y NikolaevWei Gu
Oct 16, 2003·The Journal of Biological Chemistry·Sungwoo Lee, David M Helfman
Jan 21, 2004·Nature Reviews. Cancer·Tweeny R KauPamela A Silver
Oct 12, 2004·FEBS Letters·Torsten MeissnerUwe Vinkemeier
Mar 9, 2005·Trends in Cell Biology·Ulrike Kutay, Stephan Güttinger
Dec 16, 2006·The Journal of Biological Chemistry·Allison LangeAnita H Corbett
Feb 13, 2008·Developmental Cell·Arnaud BessonJames M Roberts
Mar 21, 2008·Nature Reviews. Cancer·Isabel M ChuJoyce M Slingerland
Apr 23, 2008·Pigment Cell & Melanoma Research·C HilmiC Bertolotto
Jan 1, 2009·International Journal of Cancer. Journal International Du Cancer·Pauline J van der WattVirna D Leaner
Jun 21, 2011·Biochimica Et Biophysica Acta·Pauline J van der Watt, Virna D Leaner
Aug 16, 2011·Blood·Keiichi SakakibaraTakumi Kawabe
Oct 20, 2011·Journal of Cell Science·Mien-Chie Hung, Wolfgang Link
Jan 3, 2012·Biochemical Pharmacology·Joel G TurnerDaniel M Sullivan
Oct 20, 2012·The Journal of Urology·Hiromi InoueRobert H Weiss
Jun 26, 2013·Nature Reviews. Cancer·Eric W-F LamChuay-Yeng Koo
Nov 6, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Oriana YuLaurent Azoulay
Feb 1, 2014·Nature Reviews. Drug Discovery·David A Fruman, Christian Rommel
Apr 2, 2014·Nature Genetics·De-Chen LinH Phillip Koeffler
Jun 20, 2014·British Journal of Cancer·H SunH P Koeffler

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Citations

Jun 3, 2016·Expert Review of Anticancer Therapy·René BaumannJuergen Dunst
Jun 18, 2016·Cellular and Molecular Life Sciences : CMLS·Iraia García-SantistebanJose A Rodríguez
Jul 28, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mrinal M GounderAlbiruni Ryan Abdul Razak
Apr 12, 2018·Physiology·Fred G Pluthero, Walter H A Kahr
May 6, 2019·Journal of Clinical Medicine·David Jérémie BirnbaumFrançois Bertucci
Sep 2, 2017·Blood·Fred G Pluthero, Walter H A Kahr
Jan 21, 2020·Expert Opinion on Pharmacotherapy·Klaus PodarSundar Jagannath
Dec 24, 2019·Expert Review of Anticancer Therapy·Albert OriolAlicia Senin
Jul 1, 2016·Signal Transduction and Targeted Therapy·Qingxiang SunDa Jia
May 28, 2019·British Journal of Haematology·Andrzej J JakubowiakJeffrey A Zonder
Mar 12, 2020·Molecular & Cellular Oncology·Yaw-Dong Lang, Yuh-Shan Jou
Oct 6, 2020·Cell Cycle·Alexandre Pj Martin, Jacques H Camonis
Aug 19, 2017·Cancer Research·Fabio ConfortiGiuseppe Giaccone
Sep 2, 2021·Technology in Cancer Research & Treatment·Li-Jia PanYe-Ming Wu

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