Skip to Content
800-533-8762
  • Careers
  • Newsroom
  • Health Care Professionals
  • About Us
  • Contact Us
UPMC
  • Find a Doctor
  • Services
    • Frequently Searched Services
    • Frequently Searched Services
      Allergy & Immunology Behavioral & Mental Health Cancer Ear, Nose & Throat Endocrinology Gastroenterology Heart & Vascular Imaging Neurosciences Orthopaedics
      Physical Rehabilitation Plastic & Reconstructive Surgery Primary Care Senior Services Sports Medicine Telemedicine Transplant Surgery Walk-In Care Weight Management Women’s Health
      See all Services
    • Services by Region
    • Find a UPMC health care facility close to you quickly by browsing by region.
      UPMC in Western Pa. Western Pa. and New York
      UPMC in Central Pa. Central Pa.
      UPMC in North Central Pa. North Central Pa.
      UPMC in Western Md. Maryland & West Virginia
    • See All Services
  • Locations
    • Locations by Type
    • Locations by Type
      UPMC hospitals
      Hospitals
      Physical Therapy
      Physical Therapy
      Urgent care
      Walk-In Care
      UPMC Outpatient Centers
      Outpatient Centers
      UPMC Imaging Services
      Imaging
      Community Health Centers
      Community Health Centers
      See All Locations
    • Locations by Region
    • Locations by Region
      UPMC in Southwest Pa. Southwest Pa.
      UPMC in North Central Pa. North Central Pa.
      UPMC in Northwest Pa and Ny. Northwest Pa. & Western N.Y.
      UPMC in West Central Pa. West Central Pa.
      UPMC in Central Pa. Central Pa.
      UPMC in Western Md. Maryland & West Virginia
    • See All Locations
  • Patients & Visitors
    • Patient & Visitor Resources
    • Patient & Visitor Resources
      Patients and Visitors Resources Pay a Bill Classes & Events Medical Records Health Library Patient Information
      Patient Portals Privacy Information Shared Decision Making Traveling Patients Visitor Information
      Man uses mobile phone
      Pay a Bill
      Nurse reviews medical chart
      Request Medical Records
  • Patient Portals
  • Find Covid-19 updates
  • Schedule an appointment
  • Request medical records
  • Pay a bill
  • Learn about financial assistance
  • Find classes & events
  • Send a patient an eCard
  • Make a donation
  • Volunteer
  • Read HealthBeat blog
  • Explore UPMC Careers
Skip to Content
UPMC
  • Patient Portals
  • For Patients & Visitors
    • Find a Doctor
    • Locations
    • Patient & Visitor Resources
    • Pay a Bill
    • Services
    • More
      • Medical Records
      • Financial Assistance
      • Classes & Events
      • HealthBeat Blog
      • Health Library
  • About UPMC
    • Why UPMC
    • Facts & Stats
    • Supply Chain Management
    • Community Commitment
    • More
      • Financials
      • Support UPMC
      • UPMC Apps
      • UPMC Enterprises
      • UPMC International
  • For Health Care Professionals
    • Physician Information
    • Resources
    • Education & Training
    • Departments
    • Credentialing
  • Careers
  • Contact Us
  • Newsroom
  • UPMC >
  • Media Relations >
  • News Releases >
  • 032614 Breast Cancer Tumors Evade Drug Therapy
Media Relations
News Releases
Central Pa. News
North Central Pa. News
Contact Us
Experts
Community-Focused News
Media Kits
Media RSS
Media Relations
News Releases
Central Pa. News
North Central Pa. News
Contact Us
Experts
Community-Focused News
Media Kits
Media RSS

Chat Keywords List

  • cancel or exit: Stops your conversation
  • start over: Restarts your current scenario
  • help: Shows what this bot can do
  • terms: Shows terms of use and privacy statement
  • feedback: Give us feedback
Continue
Chat with UPMC
RESTART
MENU
CLOSE

Some Breast Cancer Tumors Hijack Patient Epigenetic Machinery to Evade Drug Therapy

Want to Make an Appointment or Need Patient Information?
Contact UPMC at

1-800-533-8762.

Go to Find a Doctor to search for a UPMC doctor.

University of Pittsburgh Schools of the Health Sciences Media Relations

3/26/2014

A breast cancer therapy that blocks estrogen synthesis to activate cancer-killing genes sometimes loses its effectiveness because the cancer takes over epigenetic mechanisms, including permanent DNA modifications in the patient’s tumor, once again allowing tumor growth, according to an international team headed by the University of Pittsburgh Cancer Institute.

The finding warrants research into adding drugs that could prevent the cancer from hijacking patients’ repressive gene regulatory machinery, which might allow the original therapy to work long enough to eradicate the tumor, the researchers report in their National Institutes of Health-funded study, published in the current issue of Science Translational Medicine.

“Our discovery is particularly notable as we enter the era of personalized medicine,” said senior author Steffi Oesterreich, Ph.D., professor in Pitt’s Department of Pharmacology and Chemical Biology and at UPCI, a partner with UPMC CancerCenter, and director of education at the Women’s Cancer Research Center. “Resistance to hormonal therapy is a major clinical problem in the treatment of most breast cancers. Through testing of a tumor’s genetic and epigenetic make-up, we may be able to identify the patients most likely to develop such resistance and, in the future, create a treatment regimen tailored to giving each patient the best chance of beating their cancer.”

Epigenetic translates to “above genetic” and is an emerging field of study that looks at how environmental factors — such as infections, pollutants, stress and, in this case, long-term exposure to drugs that block estrogen synthesis — could influence a person’s DNA. Epigenetic changes do not alter the structure of the DNA, but they do change the way the DNA is modified, which subsequently determines the potential of gene regulation.

By performing a genome-wide screen in breast cancer cells, Dr. Oesterreich and her colleagues identified a gene called HOXC10 as one that the cancer seems to modify to allow continued tumor growth in patients whose cancer becomes resistant to traditional therapies.
The hormone estrogen represses genes, such as HOXC10, that induce cell death and inhibit growth. About 70 percent of breast cancer tumors are positive for a protein called ‘estrogen receptor alpha,’ which prevents HOXC10 from killing the cancer. To overcome this, doctors put these patients on anti-estrogen therapy, including aromatase inhibitors.

Unfortunately, in some cases, the tumor uses different epigenetic mechanisms, independent of estrogen, to repress the HOXC10 gene. This allows the cancer to continue growing. When the tumor uses these mechanisms, it makes deeper modifications to the expression of the patient’s DNA, permanently blocking the HOXC10 and other genes and making cancer treatment much more difficult.
“In some patients the tumors never respond to aromatase inhibitors and just keep growing. In other patients, using aromatase inhibitors to block estrogen synthesis and allow HOXC10 and other genes to destroy the cancer works in the short term,” said Dr. Oesterreich. “But, eventually, we see the tumor start to gain ground again as the cancer permanently represses genes such as HOXC10. At that point, the aromatase inhibitor is no longer effective.”

Dr. Oesterreich and her colleagues propose that future studies look at offering a combined therapy that, along with aromatase inhibitors, also introduces drugs that modify the epigenome to prevent or delay the cancer from repressing cancer-killing genes.

The researchers also note that more investigation is needed to fully understand all the mechanisms by which HOXC10 mediates cell proliferation and death, and the roles it may play in different types of tumors.

Additional researchers on this study are Thushangi N. Pathiraja, Ph.D., Shiming Jiang, Ph.D., Yuanxin Xi, Ph.D., Jason P. Garee, Ph.D., Dean P. Edwards, Ph.D., Martin J. Shea, Rachel Schiff, Ph.D., and Wei Lei, Ph.D., all of, or formerly of, Baylor College of Medicine; Shweta Nayak, M.D., of Magee-Womens Hospital of UPMC; Adrian V. Lee, Ph.D., Jian Chen, M.S., and Nancy E. Davidson, M.D., all of UPCI; Richard J. Santen, M.D., of the University of Virginia; Frank Gannon, Ph.D., and Sara Kangaspeska, Ph.D., formerly of the European Molecular Biology Laboratory and now at QIMR Berghofer Medical Research Institute in Brisbane, Australia, and at Institute for Molecular Medicine, Helsinki, Finland; Jaroslav Jelinek, M.D., Ph.D., and Jean-Pierre J. Issa, M.D., both of Temple University; Jennifer K. Richer, Ph.D., and Anthony Elias, M.D., both of the University of Colorado; and Marie McIlroy, Ph.D., and Leonie Young, Ph.D., both of the Royal College of Surgeons of Ireland.

This project was funded in part by the Alexander von Humboldt Foundation; U.S. Department of Defense grant 5W81XWH-06-1-0713; National Institutes of Health grants P30CA125123, P30CA47904, P50CA58183, P01CA030195, R01HG007538, R01CA94118 and R01CA097213; Susan G. Komen for the Cure Foundation grant PG12221410; the EIF/Lee Jeans Breast Cancer Research Program; Su2C/Breast Cancer Program; Breast Cancer Research Foundation; and Pennsylvania Department of Health.

UPMC
200 Lothrop Street Pittsburgh, PA 15213

412-647-8762 800-533-8762

Patients And Visitors
  • Find a Doctor
  • Locations
  • Pay a Bill
  • Patient & Visitor Resources
  • Disabilities Resource Center
  • Services
  • Medical Records
  • No Surprises Act
  • Price Transparency
  • Financial Assistance
  • Classes & Events
  • Health Library
Health Care Professionals
  • Physician Information
  • Resources
  • Education & Training
  • Departments
  • Credentialing
Newsroom
  • Newsroom Home
  • Inside Life Changing Medicine Blog
  • News Releases
About
  • Why UPMC
  • Facts & Stats
  • Supply Chain Management
  • Community Commitment
  • Financials
  • Supporting UPMC
  • HealthBeat Blog
  • UPMC Apps
  • UPMC Enterprises
  • UPMC Health Plan
  • UPMC International
  • Nondiscrimination Policy
Life changing is...
Follow UPMC
  • Contact Us
  • Website/Email Terms of Use
  • Medical Advice Disclaimer
  • Privacy Information
  • Active Privacy Alerts
  • Sitemap
© 2025 UPMC I Affiliated with the University of Pittsburgh Schools of the Health Sciences Supplemental content provided by Healthwise, Incorporated. To learn more, visit healthwise.org
Find Care
Providers
Video Visit
Portal Login