Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Tumor Biology 23: In Vivo Imaging 3

Assesment of EGFR somatic kinase domain mutant tumor response to erlotinib using FDG-PET imaging

Kendall Carey, Annie Ogasawara, Maria Romero, Jed Ross, Leanne McFarland and Simon Williams
Kendall Carey
Genentech, Inc., South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annie Ogasawara
Genentech, Inc., South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria Romero
Genentech, Inc., South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jed Ross
Genentech, Inc., South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leanne McFarland
Genentech, Inc., South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon Williams
Genentech, Inc., South San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published April 2006
  • Article
  • Info & Metrics
Loading
Proc Amer Assoc Cancer Res, Volume 47, 2006

Abstract

3466

Somatic mutations in the epidermal growth factor receptor (EGFR) have been identified in non-small lung cancer patients and are correlated with enhanced sensitivity to the tyrosine kinase domain inhibitor erlotinib (OSI-774, TarcevaR). Erlotinib is a selective, orally available competitive inhibitor for ATP binding to the EGFR tyrosine kinase domain and has been approved for use in the treatment of advanced non-small cell lung cancer for patients who have failed at least one prior chemotherapy regimen. To evaluate the biological role of EGFR somatic mutations and the influence of these mutations on erlotinib sensitivity, we have generated stable NR6 cell lines expressing equivalent levels of EGFR, and two clinically detected EGFR somatic mutations, EGFR-L858R and EGFR-Del(746-752). NR6 cells do not express EGFR or detectable levels of ErbB2, ErbB3, or ErbB4. Both the EGFR-L858R and EGFR-Del(746-752) mutations facilitate ligand-dependent anchorage-independent growth in soft agar, confer a higher proliferative rate, form tumors in immune compromised mice, and are differentially sensitive to erlotinib compared to wild-type EGFR both in vivo and in vitro. In this study, we have used positron emission tomography (PET) imaging of 2-fluoro-2-deoxy-D-glucose (FDG) uptake to evaluate the difference in metabolic activity of EGFR, EGFR-L858R, and EGFR-Del(746-750) expressing tumors in immune deficient mice. Tumors expressing wild-type and mutant EGFR have similar glucose uptake rates except after a period of overnight fasting where tumors expressing EGFR kinase domain mutations demonstrate a 2-fold increase in FDG uptake compared to wild-type EGFR tumors (p=0.001). 3H-FDG uptake in EGFR expressing cells is significantly higher compared to the NR6 parental cell line and erlotinib differentially inhibits glucose uptake in vitro for EGFR compared to EGFR-L858R and EGFR Del(746-752) (IC50=175nM, 85nM, and 9nM respectively). We find that FDG-PET is useful for evaluating the sensitivity of these mutations and the EGFR Del(746-752) and L858R mutations are significantly more sensitive to erlotinib compared to wild-type EGFR tumors. At the maximally effective dose of erlotinib (150mg/kg), the normalized glucose uptake decreased by 33% at 24 hours post-treatment and 57% at 48 hours in the tumors expressing EGFR-Del(746-752) compared with no significant decrease in the EGFR tumors. Our data indicate that EGFR somatic mutations influence EGFR signaling pathways that modulate glucose metabolism. These findings suggest FDG-PET is a sensitive method to evaluate the effects of small molecule kinase inhibitors and may be useful in evaluating clinical responders to erlotinib therapy.

  • American Association for Cancer Research
Previous
Back to top
Cancer Research: 66 (8 Supplement)
April 2006
Volume 66, Issue 8 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Assesment of EGFR somatic kinase domain mutant tumor response to erlotinib using FDG-PET imaging
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Assesment of EGFR somatic kinase domain mutant tumor response to erlotinib using FDG-PET imaging
Kendall Carey, Annie Ogasawara, Maria Romero, Jed Ross, Leanne McFarland and Simon Williams
Cancer Res April 15 2006 (66) (8 Supplement) 813;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Assesment of EGFR somatic kinase domain mutant tumor response to erlotinib using FDG-PET imaging
Kendall Carey, Annie Ogasawara, Maria Romero, Jed Ross, Leanne McFarland and Simon Williams
Cancer Res April 15 2006 (66) (8 Supplement) 813;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Biological characterization and non invasive PET imaging explorations of lymphatic dissemination in a human melanoma xenograft model
  • Dynamic noninvasive tracking of response of endothelial cells to hypoxia and cancer cells using MRI
  • Metabolic charcterisation by in vivo Proton Magnetic Resonance Spectroscopy (PMRS) -future non-invasive biopsy to grade soft tissue sarcoma?
Show more Tumor Biology 23: In Vivo Imaging 3
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2019 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement