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
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • 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
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Experimental and Molecular Therapeutics

Abstract 3603: Molecular targeting of cetuximab resistant head and neck cancer

Adam D. Swick, Dana Gunderson, Molly Smith, Grace Blitzer, Andrew Stein, Kwangok P. Nickel and Randall J. Kimple
Adam D. Swick
University of Wisconsin, Madison, WI.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dana Gunderson
University of Wisconsin, Madison, WI.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Molly Smith
University of Wisconsin, Madison, WI.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grace Blitzer
University of Wisconsin, Madison, WI.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Stein
University of Wisconsin, Madison, WI.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kwangok P. Nickel
University of Wisconsin, Madison, WI.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Randall J. Kimple
University of Wisconsin, Madison, WI.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM2015-3603 Published August 2015
  • Article
  • Info & Metrics
Loading
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Abstract

Despite promising preclinical data, the EGFR targeted monoclonal antibody, cetuximab, has limited use as single agent therapy in the treatment of head and neck cancer due to the development of therapeutic resistance. Improved approaches to treat these cancers will need to address the evolving molecular landscape of head and neck cancer. Recent reports describing mutations or copy number alterations in PI3K and PTEN as potential causes of cetuximab resistance have sparked interest in therapeutics that target these pathways as alternatives to or in combination with EGFR targeting drugs.

Using both in vitro and in vivo models of head and neck squamous cell carcinoma (HNSCC) we have recapitulated the diversity of responses to cetuximab observed in the patient population and are testing alternative therapies. Examining an array of HNSCC cell lines, including both human papillomavirus (HPV) positive and negative lines, we observed a wide range of sensitivities to this drug, with little to no growth inhibition in some lines even at micromolar concentrations. For lines that were sensitive to drug, effective growth inhibition, demonstrated in both proliferation and colony formation assays, was linked with suppressed phosphorylation of both Akt and ERK/MAPK signaling downstream of EGFR. Additionally, in the sensitive HPV+ HNSCC lines, cetuximab treatment induced apoptosis marked by caspase activity. Both sensitive and resistant HNSCC lines were then tested for response to both AZD8055, a dual mTORC1/2 inhibitor and BEZ235, a PI3K/mTORC1 inhibitor, resulting in both growth inhibition and successful suppression of phosphorylation of their Akt and S6 targets, suggesting that these drugs may be useful alternatives or adjuvants for cetuximab treatment.

In vivo models of HNSCC were also utilized to test the efficacy of cetuximab treatment and begin to evaluate alternative or combination therapies. Using immunocompromised mouse models, both cell line xenografts and novel patient derived xenografts presented a range of sensitivities to cetuximab. In an effort to identify potential biomarkers that would predict response to cetuximab, IHC staining of pre-treatment tumor samples was carried out and demonstrated that low phospho-Akt and phospho-ERK levels correlated with cetuximab sensitivity. Initial in vivo studies using the PI3K/mTORC inhibitors AZD8055 and BEZ235 to treat both cetuximab sensitive and resistant xenografts, have shown that these compounds may be effective at suppressing growth in both categories of tumors. These studies provide initial pre-clinical data to support the use of PI3K inhibition for the treatment of head and neck cancer.

Citation Format: Adam D. Swick, Dana Gunderson, Molly Smith, Grace Blitzer, Andrew Stein, Kwangok P. Nickel, Randall J. Kimple. Molecular targeting of cetuximab resistant head and neck cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3603. doi:10.1158/1538-7445.AM2015-3603

  • ©2015 American Association for Cancer Research.
Previous
Back to top
Cancer Research: 75 (15 Supplement)
August 2015
Volume 75, Issue 15 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.
Abstract 3603: Molecular targeting of cetuximab resistant head and neck cancer
(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
Abstract 3603: Molecular targeting of cetuximab resistant head and neck cancer
Adam D. Swick, Dana Gunderson, Molly Smith, Grace Blitzer, Andrew Stein, Kwangok P. Nickel and Randall J. Kimple
Cancer Res August 1 2015 (75) (15 Supplement) 3603; DOI: 10.1158/1538-7445.AM2015-3603

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract 3603: Molecular targeting of cetuximab resistant head and neck cancer
Adam D. Swick, Dana Gunderson, Molly Smith, Grace Blitzer, Andrew Stein, Kwangok P. Nickel and Randall J. Kimple
Cancer Res August 1 2015 (75) (15 Supplement) 3603; DOI: 10.1158/1538-7445.AM2015-3603
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

Experimental and Molecular Therapeutics

  • Abstract SY14-03: Anaplastic lymphoma kinase (ALK): Normal biology and role in hematopoietic malignancies
  • Abstract SY18-01: Targeting the p53-MDM2 interaction for cancer therapy
  • Abstract SSY01-04: Discovery and validation of genome-wide genetic signatures of chemotherapy susceptibility: A translational model
Show more 3

Poster Presentations - Proffered Abstracts

  • Abstract LB-236: Risk of tMDS/AML after chemotherapy for first primary lymphoid malignancy, 2000-2013
  • Abstract LB-001: Impact of direct physician engagement with racial/ethnic minorities for oncology clinical trial access and accrual model
  • Abstract LB-107: EV-TRACK: transparent reporting and centralizing knowledge of extracellular vesicles to support the validation of extracellular vesicle biomarkers in cancer research
Show more 3

Poster Presentations - Resistance to Pathway-Targeted Therapeutics 2

  • Abstract 3599: Resistance mechanisms to HER2-targeting treatment in HER2-positive gastric cancer
  • Abstract 3594: P-glycoprotein attenuates Src activation and DNA repair activity via increased C-terminal Src kinase-binding protein, a negative regulator of Src, in multidrug-resistant cells
  • Abstract 3581: Rapid conversion to resistance, of a colon PDX with ret-fusion, by ponatinib treatment could potentially be attributed to the introduction of the gate keeper mutation V804M
Show more 3
  • Home
  • Alerts
  • Feedback
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 © 2018 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