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 2634: Investigating the chemotherapeutic effects of aspirin in mutant PIK3CA breast cancer

Whitney Henry and Alex Toker
Whitney Henry
Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alex Toker
Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.AM2015-2634 Published August 2015
  • Article
  • Info & Metrics
Loading
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Abstract

Although aspirin is primarily administered as an antipyretic and analgesic, numerous observational and randomized clinical trials have suggested a potential chemotherapeutic use. Recently, two independent studies demonstrated that aspirin use is associated with superior survival in colorectal cancer patients with mutant-PIK3CA but not among those with the wild-type gene. Despite these seminal observations, the molecular basis for this phenomenon remains poorly understood. Furthermore, whether this observation occurs in breast cancer is unknown. Given that (1) mutation of PIK3CA, the gene encoding the catalytic subunit of the phosphoinositide 3-kinase (PI 3-K) is highly prevalent in breast cancer and that (2) aspirin use is associated with a decrease in breast cancer mortality and distant recurrence, the relationship between PI 3-K pathway activation and the protective benefit of aspirin in breast cancer was investigated. Here, we utilize both PIK3CA mutant breast cancer cell lines and a well-characterized system of immortalized mammary epithelial cells stably expressing either wild-type and mutant PIK3CA E545K and H1047R respectively. Mutant PIK3CA breast cancer cells show a dose-dependent decrease in cell viability with increasing concentration of aspirin/salicylate. In these cells, co-treatment of aspirin with PI 3-K pathway inhibitors BYL719 or BKM120 caused a more significant decrease on cell growth compared to each single agent alone. In 3D culture, MCF10A cells expressing mutant PIK3CA-H1047R showed greater sensitivity to aspirin compared to cells expressing wild-type PIK3CA. Gene expression profiling and quantitative qRT-PCR was employed to identify and validate mutant PIK3CA-regulated genes respectively. Many of these genes were associated with inflammation; among them was the PTGS2 gene which encodes for cyclooxygenase-2 (COX-2). We observed that mutant PIK3CA regulates cyclooxygenase-2 (COX-2) mRNA and protein expression as well as production of prostaglandin E2α (PGE2α). Expression of mutant PIK3CA also increases phosphorylation of IKKβ and IκB; increases mTORC1 signaling and reduces AMPK activity. This is abrogated upon pharmacologic inhibition of mutant PIK3CA with BYL719 and BKM120. Notably, both aspirin and its metabolite salicylate can inhibit these PIK3CA-induced pathways and activate AMPK signaling. An understanding of these key survival and metabolic signaling pathways, which are modulated by aspirin, may help to explain aspirin's beneficial effect in PIK3CA-mutant breast cancers. Given the growing interest in personalized medicine, this pre-clinical study may provide insight for the stratification of patients who are most likely to benefit from adjuvant aspirin therapy.

Citation Format: Whitney Henry, Alex Toker. Investigating the chemotherapeutic effects of aspirin in mutant PIK3CA breast 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 2634. doi:10.1158/1538-7445.AM2015-2634

  • ©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 2634: Investigating the chemotherapeutic effects of aspirin in mutant PIK3CA breast 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 2634: Investigating the chemotherapeutic effects of aspirin in mutant PIK3CA breast cancer
Whitney Henry and Alex Toker
Cancer Res August 1 2015 (75) (15 Supplement) 2634; DOI: 10.1158/1538-7445.AM2015-2634

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract 2634: Investigating the chemotherapeutic effects of aspirin in mutant PIK3CA breast cancer
Whitney Henry and Alex Toker
Cancer Res August 1 2015 (75) (15 Supplement) 2634; DOI: 10.1158/1538-7445.AM2015-2634
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 - Oncogenes, Tumor Suppressor Genes, and Gene Products as Targets for Therapy

  • Abstract 2647: Anti-tumor activity of sHA8k, a HYAL1 hyaluronidase inhibitor, in bladder cancer cells
  • Abstract 2643: Small molecule identification for the restoration of p53 pathway through p73 and by degradation of mutant p53
  • Abstract 2642: EF2-kinase (EF2K): A novel molecular target in ovarian and pancreatic cancers
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