Aberrant activation of the mTOR pathway and anti-tumour effect of everolimus on oesophageal squamous cell carcinoma.

British Journal of Cancer
K HirashimaH Baba

Abstract

The mammalian target of rapamycin (mTOR) protein is important for cellular growth and homeostasis. The presence and prognostic significance of inappropriate mTOR activation have been reported for several cancers. Mammalian target of rapamycin inhibitors, such as everolimus (RAD001), are in development and show promise as anti-cancer drugs; however, the therapeutic effect of everolimus on oesophageal squamous cell carcinoma (OSCC) remains unknown. Phosphorylation of mTOR (p-mTOR) was evaluated in 167 resected OSCC tumours and 5 OSCC cell lines. The effects of everolimus on the OSCC cell lines TE4 and TE11 in vitro and alone or in combination with cisplatin on tumour growth in vivo were evaluated. Mammalian target of rapamycin phosphorylation was detected in 116 tumours (69.5%) and all the 5 OSCC cell lines. Everolimus suppressed p-mTOR downstream pathways, inhibited proliferation and invasion, and induced apoptosis in both TE4 and TE11 cells. In a mouse xenograft model established with TE4 and TE11 cells, everolimus alone or in combination with cisplatin inhibited tumour growth. The mTOR pathway was aberrantly activated in most OSCC tumours. Everolimus had a therapeutic effect both as a single agent and in combination with cispl...Continue Reading

References

Sep 23, 2000·Nature·P Carmeliet, R K Jain
Sep 26, 2003·Cancer Biology & Therapy·Monica M MitaEric K Rowinsky
Dec 6, 2003·The New England Journal of Medicine·Peter C Enzinger, Robert J Mayer
May 4, 2004·Nature Reviews. Cancer·Mary-Ann Bjornsti, Peter J Houghton
Nov 19, 2004·Neoplasia : an International Journal for Oncology Research·Donatella Del BufaloGabriella Zupi
Dec 1, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michele MilellaGabriella Zupi
Dec 27, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Roberto BiancoGiampaolo Tortora
Sep 5, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karen W L YeeFrancis J Giles
Sep 14, 2006·Cancer Biology & Therapy·Janet E Dancey
Oct 17, 2006·Oncogene·J B Easton, P J Houghton
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert T Abraham, James J Gibbons
Jul 20, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Seiji MabuchiJoseph R Testa
Aug 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bruce E JohnsonPasi A Jänne
Aug 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Beata HerbergerMartin Filipits
Oct 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maryam FouladiWayne L Furman
Nov 28, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ahmad AwadaMartine Piccart
Feb 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Philipp C ManegoldChristiane J Bruns
Mar 12, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Chiaki TanakaHeidi A Lane
Mar 12, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Josep TaberneroJosé Baselga
Mar 12, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anne O'DonnellIan Judson
May 14, 2008·Journal of Clinical Pathology·J BooneR van Hillegersberg
Sep 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James C YaoFunda Meric-Bernstam
Oct 11, 2008·Nature Reviews. Cancer·Bradly G Wouters, Marianne Koritzinsky
Dec 3, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian M WolpinCharles S Fuchs
Feb 19, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Heidi A LaneTerence O'Reilly
Apr 30, 2009·Cancer·Gary R Hudes
May 30, 2009·Current Oncology·A Kapoor
Jun 26, 2009·Nature·Kenneth L ScottLynda Chin
Sep 1, 2009·Cancer Letters·Emmanuel S AntonarakisMario A Eisenberger
Dec 4, 2009·Oncogene·S Menon, B D Manning
May 27, 2010·British Journal of Cancer·P WorkmanUNKNOWN Committee of the National Cancer Research Institute
Jun 10, 2010·Journal of Cell Communication and Signaling·Kristina C WiesmanJohn J Castellot

❮ Previous
Next ❯

Citations

Mar 4, 2014·Critical Reviews in Oncology/hematology·Amr MohamedNabil F Saba
Nov 26, 2013·Clinical Medicine Insights. Therapeutics·Kelsey P Pendleton, Jennifer R Grandis
Aug 23, 2018·Journal of Cellular Biochemistry·Xuefeng ZhouJinping Zhao
Dec 3, 2013·Chemical & Pharmaceutical Bulletin·Yoshiharu Iwabuchi
Oct 10, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Angel ChaoChyong-Huey Lai
May 6, 2015·Transplant International : Official Journal of the European Society for Organ Transplantation·Catarina CanhaIgnacio Revuelta
May 18, 2013·Current Opinion in Oncology·Patrick M Boland, Barbara Burtness
Feb 15, 2014·Oncology Letters·Penpak MoolthiyaKawin Leelawat
Oct 9, 2020·Signal Transduction and Targeted Therapy·Yan-Ming YangBin Li
Nov 26, 2013·Cancer Research·Hiroshi SawayamaHideo Baba
Mar 26, 2015·Molecular Cancer Research : MCR·Satoshi IdaMasaki Ohmuraya
Sep 4, 2021·Experimental and Therapeutic Medicine·Tao LiuShengzhuang Yang

❮ Previous
Next ❯

Methods Mentioned

BETA
surgical resection
electrophoresis
flow cytometry
xenograft

Software Mentioned

Stat View - J

Related Concepts

Related Feeds

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

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.