Targeting endoplasmic reticulum stress and Akt with OSU-03012 and gefitinib or erlotinib to overcome resistance to epidermal growth factor receptor inhibitors.

Cancer Research
Yu-Chieh WangChing-Shih Chen

Abstract

Preexisting and acquired resistance to epidermal growth factor receptor (EGFR) inhibitors limits their clinical usefulness in patients with advanced non-small cell lung cancer (NSCLC). This study characterizes the efficacy and mechanisms of the combination of gefitinib or erlotinib with OSU-03012, a celecoxib-derived antitumor agent, to overcome EGFR inhibitor resistance in three NSCLC cell lines, H1155, H23, and A549. The OSU-03012/EGFR inhibitor combination induced pronounced apoptosis in H1155 and H23 cells, but not in A549 cells, suggesting a correlation between drug sensitivity and basal phospho-Akt levels independently of EGFR expression status. Evidence indicates that this combination facilitates apoptosis through both Akt signaling inhibition and up-regulation of endoplasmic reticulum (ER) stress-induced, GADD153-mediated pathways. For example, ectopic expression of constitutively active Akt significantly attenuated the inhibitory effect on cell survival, and small interfering RNA-mediated knockdown of GADD153 protected cells from undergoing apoptosis in response to drug cotreatments. Furthermore, the OSU-03012/EGFR inhibitor combination induced GADD153-mediated up-regulation of death receptor 5 expression and subsequen...Continue Reading

References

May 23, 1998·Genes, Chromosomes & Cancer·T KohnoJ Yokota
Oct 30, 1998·Oncogene·E ForgacsJ D Minna
Dec 18, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·J Klastersky, M Paesmans
Sep 14, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Roy S HerbstPatricia Mucci LoRusso
Jul 31, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antoinette R TanSandra M Swain
Aug 24, 2004·The Journal of Biological Chemistry·Hirohito Yamaguchi, Hong-Gang Wang
Oct 12, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wells A MessersmithManuel Hidalgo
Dec 1, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·W Jeffrey PettyEthan Dmitrovsky
Dec 2, 2004·Journal of the National Cancer Institute·Xiangguo LiuShi-Yong Sun
Feb 25, 2005·The New England Journal of Medicine·Susumu KobayashiBalázs Halmos
May 18, 2005·Biochemical and Biophysical Research Communications·Motoyasu SajiMatthew D Ringel
Jul 15, 2005·The New England Journal of Medicine·Ming-Sound TsaoFrances A Shepherd
Sep 21, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lori J WirthMarshall R Posner
Oct 14, 2005·Expert Review of Anticancer Therapy·Ewan R Brown, Frances A Shepherd
Dec 6, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jian-Min TangXiu-Jun Chang
Dec 17, 2005·Cancer Research·Steffan T NawrockiDavid J McConkey
Feb 4, 2006·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·Junan LiPeter Muscarella
Feb 10, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Esther CondeMontserrat Sanchez-Cespedes
Feb 14, 2006·Current Molecular Medicine·Jianze Li, Amy S Lee
Mar 22, 2006·The Oncologist·Paolo MaioneFortunato Ciardiello
Mar 30, 2006·British Journal of Cancer·C A TownsleyA M Oza
Apr 7, 2006·Carcinogenesis·Su-Hyeong KimYong-Sang Song
May 26, 2006·Nature·Reuben J Shaw, Lewis C Cantley
Jun 3, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karen L ReckampRobert A Figlin

❮ Previous
Next ❯

Citations

Nov 4, 2010·Breast Cancer Research and Treatment·Caroline Brünner-KubathThomas W Grunt
Oct 7, 2009·Antimicrobial Agents and Chemotherapy·Hao-Chieh ChiuChing-Shih Chen
Apr 12, 2012·Molecular Cancer Therapeutics·Neil E BholaJennifer R Grandis
Sep 25, 2012·Biochemical Pharmacology·Axel H Schönthal
Apr 11, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Tina X LeeLong-Sheng Chang
Jan 23, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jen-Chung KoYun-Wei Lin
Mar 14, 2009·The Journal of Investigative Dermatology·Kazumitsu SugiuraJiro Usukura
Aug 26, 2009·Chemical Biology & Drug Design·Leyte L WinfieldDayle M Smith
May 31, 2014·Experimental Cell Research·Cheng-Yi ChangChun-Jung Chen
Apr 17, 2012·Otolaryngologia polska. The Polish otolaryngology·Craig MillerAbraham Jacob
Oct 23, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jeffrey G DickhoutRichard C Austin
Sep 4, 2015·The Journal of Pharmacology and Experimental Therapeutics·Cyril SobolewskiMarc Diederich
Aug 27, 2018·Molecular and Cellular Biochemistry·Peter NguyenDeepali Bhandari
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Victor J T LinYu-Chieh Wang
May 8, 2021·Drug Design, Development and Therapy·Leilei DingJie Lu
May 11, 2019·Experimental Cell Research·Daniel W ColeAndrew M Fribley

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis