American Association for Cancer Research

Dream Team: An Integrated Approach to Targeting Breast Cancer Molecular Subtypes and Their Resistance Phenotypes

 

Overview:

Although a great deal of progress has been made in understanding and treating breast cancer, over 40,000 women a year lose their lives to this disease in the United States alone. During the past several years, researchers have come to understand that breast cancer is not a single disease but rather a spectrum of conditions that vary in their biology and response to treatment, and understanding breast cancer's molecular diversity has been the driving force leading to the development of new treatments for this disease.

Researchers are rapidly moving beyond the "one size fits all" approach into a new era in which breast cancer treatments will be tailored to the biology of the tumor. This project will address the most significant issues related to the three major subtypes of breast cancer — ER positive, HER2 positive and triple negative (ER negative, PR negative and HER2 negative) and will use that information to develop innovative, less toxic therapies with the potential to improve the treatment outcomes for women with this disease.

One of the primary obstacles to effective cancer treatment is the ability of cancer cells to become resistant to treatments that are initially effective. Over a period of time, cancer cells are able to develop ways of "outsmarting" the drugs and agents designed to kill them. This Dream Team will study the driving mechanisms that lead to resistance in the three major breast cancer subtypes. Understanding resistance opens the door to developing innovative therapeutic agents that overcome this critical problem.

Another area of interest is in the role that cancer stem cells play in resistance. Researchers now realize that the growth and spread of many cancers, including breast cancers, are influenced by the existence of these stem cells which are often highly resistant to otherwise effective treatments. The Team will study the ways in which this unique malignant cell population operates across the three major breast cancer subtypes, knowledge that could be important to the developing new treatments for breast as well as other major cancers.

One critical component of this study will be to bring together the vast amount of information that exists about breast cancer into an integrated data base that will form a "discovery platform," or basis for identifying and validating new drug combinations and targets that can be pursued in clinical trials. The Team expects that these efforts will lead to significantly improved therapies for breast cancer, especially the most difficult to treat forms, within the three year period.

Specific Research Goals:

  • Develop innovative, less toxic therapies with the potential to improve the treatment outcomes for women with the three major subtypes of breast cancer.
  • Study ways in which the malignant cancer stem cells impact resistance across the three major breast cancer subtypes, important data required to develop new treatments for breast and other major cancers.
  • Develop a "discovery platform" (a basis for identifying and validating new drug combinations and targets that can be pursued in clinical trials) by creating a database that integrates existing information about breast cancer.

Project Status:

This Dream Team is studying three subtypes of breast cancer to understand how they become resistant to targeted drugs. They are examining mechanisms of drug resistance at a molecular level to understand how to avoid or to completely circumvent the cancer's defenses. They are moving forward to evaluate and test drugs and new drug combinations to find the ones that should and can be tested on patients with specific cancer subtypes in clinical trials. A state-of-the-art information platform has been established that uses systems biology approaches to catalog and mine breast cancer data gathered from several resources.

Amount of Funding:
$16.5 million

Leaders:
Joe W. Gray, Ph.D., Chair, Department of Biomedical Engineering, Oregon Health and Science University
Dennis J. Slamon, M.D., Ph.D., director of clinical/translational research at the University of California Los Angeles, Jonsson Comprehensive Cancer Center

Principals:
Alan Ashworth, FRS, Ph.D., director, Breakthrough Breast Cancer, The Institute of Cancer Research
Joan S. Brugge, Ph.D., professor and chair, Cell Biology, Harvard Medical School
Arul M. Chinnaiyan, M.D., Ph.D., director, Michigan Center for Translational Pathology, University of Michigan
Gregory J. Hannon, Ph.D., professor, Watson School of Biological Sciences, Cold Spring Harbor Laboratory
David Haussler, Ph.D., investigator, Howard Hughes Medical Institute, University of California, Santa Cruz 
V. Craig Jordan, OBE, Ph.D., D.Sc., scientific director, Vincent T. Lombardi Comprehensive Cancer Center, Georgetown University [July 1]
C. Kent Osborne, M.D., director, Dan L. Duncan Cancer Center and Lester and Sue Smith Breast Center, Baylor College of Medicine
Peter K. Sorger, Ph.D., professor, systems biology, Harvard Medical School
Terry P. Speed, Ph.D., professor, department of statistics, University of California
Zena Werb, Ph.D., professor and vice-chair, department of anatomy, Helen Diller Comprehensive Cancer Center
Max S. Wicha, M.D., director, University of Michigan Comprehensive Cancer Center


Advocates:
Janice Barlow
Cindy Geoghegan
Ellen L. Stovall
Fran M. Visco

 

Date page last updated: Sept. 12, 2011