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

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CEBP Focus Archive
    • Meeting Abstracts
    • Progress and Priorities
    • Collections
      • COVID-19 & Cancer Resource Center
      • Disparities Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Informing Public Health Policy
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • 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
  • My Cart

Search

  • Advanced search
Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CEBP Focus Archive
    • Meeting Abstracts
    • Progress and Priorities
    • Collections
      • COVID-19 & Cancer Resource Center
      • Disparities Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Informing Public Health Policy
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Epidemiology, Lifestyle, and Genetics

Abstract IA19: Regulation of 53BP1 in BRCA1-deficient cells: Why vitamin D matters and how disparities in vitamin D levels could promote aggressive TNBC in women of color

Susana Gonzalo
Susana Gonzalo
St. Louis University School of Medicine, St. Louis, MO.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7755.DISP14-IA19 Published October 2015
  • Article
  • Info & Metrics
Loading
Abstracts: Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; November 9-12, 2014; San Antonio, TX

Abstract

Breast cancer is the leading cause of cancer death in women worldwide. BRCA1-deficient and triple-negative breast cancers (TNBC) are particularly aggressive, strike younger, Hispanic and African American women, and are most difficult to treat. These tumors exhibit DNA repair defects, making them vulnerable to DNA damaging therapies. Currently, the most promising therapeutic agents are poly(ADP-ribose) polymerase inhibitors (PARPi), which render cells already deficient in DNA repair, with an unbearable load of DNA damage. Excitement about PARPi has been fueled by clinical trials showing that these compounds, either as single agents or in combination with chemotherapy, have very encouraging outcomes in BRCA1-related and TNBC and with minimal toxicity. However, a significant fraction of these cancers acquire resistance to PARPi. Understanding the molecular mechanisms that confer PARPi resistance will have a big therapeutic impact.

Elegant studies demonstrated that loss of the DNA repair factor 53BP1 contributes to progression of BRCA1-deficient and TNBC and to their resistance to PARPi. Thus, raising the levels of 53BP1 in these tumors could represent a new therapeutic strategy. Our team identified a new pathway modulating the levels of 53BP1, which could be exploited to stabilize protein levels. We found that BRCA1-deficient cells activate the degradation of 53BP1 by the protease cathepsin-L (CTSL), and that CTSL inhibition by vitamin D stabilizes 53BP1, reduces proliferation, and increases PARPi and radiation sensitivity. Our studies in human breast tumors also suggest that deficiencies in vitamin D/vitamin D receptor (VDR) axis, more prevalent in women of color, could underlie the activation of CTSL-mediated degradation of 53BP1 in BRCA1-deficient and TNBC. Our current studies are testing the ability of vitamin D treatment to reduce the growth of BRCA1-deficient and TNBC cells, as well as their resistance to PARPi, providing a novel modality of treatment for these cancer patients.

Citation Format: Susana Gonzalo. Regulation of 53BP1 in BRCA1-deficient cells: Why vitamin D matters and how disparities in vitamin D levels could promote aggressive TNBC in women of color. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA19.

  • ©2015 American Association for Cancer Research.
Previous
Back to top
Cancer Epidemiology Biomarkers & Prevention: 24 (10 Supplement)
October 2015
Volume 24, Issue 10 Supplement
  • Table of Contents

Sign up for alerts

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

Thank you for sharing this Cancer Epidemiology, Biomarkers & Prevention 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 IA19: Regulation of 53BP1 in BRCA1-deficient cells: Why vitamin D matters and how disparities in vitamin D levels could promote aggressive TNBC in women of color
(Your Name) has forwarded a page to you from Cancer Epidemiology, Biomarkers & Prevention
(Your Name) thought you would be interested in this article in Cancer Epidemiology, Biomarkers & Prevention.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract IA19: Regulation of 53BP1 in BRCA1-deficient cells: Why vitamin D matters and how disparities in vitamin D levels could promote aggressive TNBC in women of color
Susana Gonzalo
Cancer Epidemiol Biomarkers Prev October 1 2015 (24) (10 Supplement) IA19; DOI: 10.1158/1538-7755.DISP14-IA19

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract IA19: Regulation of 53BP1 in BRCA1-deficient cells: Why vitamin D matters and how disparities in vitamin D levels could promote aggressive TNBC in women of color
Susana Gonzalo
Cancer Epidemiol Biomarkers Prev October 1 2015 (24) (10 Supplement) IA19; DOI: 10.1158/1538-7755.DISP14-IA19
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

Epidemiology, Lifestyle, and Genetics

  • Abstract A51: Disparities in cervical cancer patients by race and histology
  • Abstract A35: An integrative model of cancer disparities based on the calcium molecular theory of carcinogenesis
  • Abstract A92: Black race is associated with worse distant relapse-free survival in breast cancer patients treated with neoadjuvant compared to adjuvant systemic chemotherapy
Show more Epidemiology, Lifestyle, and Genetics

Diet and Nutrition

  • Abstract B50: A church-based diet, physical activity, and stress intervention results in lower waist to hip ratios and reduced chronic inflammation in African-American males
  • Abstract B52: Describing Adherence to Dietary Guidelines in Overweight African American Breast Cancer Survivors
  • Abstract B51: Dairy, calcium, vitamin D and ovarian cancer risk in African-American women
Show more Diet and Nutrition

Diet and Nutrition: Oral Presentations - Invited Abstracts

  • Abstract ED02-02: Vitamin D status as a measure of chronic disease risk
Show more Diet and Nutrition: Oral Presentations - Invited Abstracts
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Epidemiology, Biomarkers & Prevention

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

Copyright © 2021 by the American Association for Cancer Research.

Cancer Epidemiology, Biomarkers & Prevention
eISSN: 1538-7755
ISSN: 1055-9965

Advertisement