June 9, 2009

New Breast Cancer Treatments May Stem from $16.5 Million Award

A UCSF research pioneer in breast cancer – a disease that still kills about 40,000 US women each year – will co-lead a new, $16.5 million effort to develop more effective, targeted therapies to vanquish various types of breast tumors, including cancers that are particularly unresponsive to current treatments.

Joe Gray. Photo by Majed Abolfazli

Joe Gray, PhD, director of the Life Sciences Division at the Lawrence Berkeley National Laboratory and leader of the Breast Oncology Program at the UCSF Helen Diller Family Comprehensive Cancer Center, will help spearhead the effort. The three-year, $16.5 million award was made by Stand Up to Cancer, an Entertainment Industry Foundation charitable organization. Working with the American Association for Cancer Research, the foundation awarded a total of $73.6 million to five research teams, each boasting extensive depth and breadth of scientific expertise. With Dennis Slamon, MD, PhD, director of clinical/translational research at UCLA’s Jonsson Comprehensive Cancer Center, Gray co-leads what has been dubbed the Breast Cancer Dream Team. Thirteen leading scientists are taking part. Thanks to large-scale, government-funded efforts such as the Human Genome Project, scientists have gained a significant understanding about how specific genes and molecules can go awry and contribute to the formation of potentially deadly tumors. “We’ve made significant progress in our understanding of the molecular basis of cancer,” Gray says. “We know now that breast cancer is not one disease. It’s a collection of several different diseases.” The abnormal genes and proteins driving cancer growth can vary from tumor to tumor. The goal now is to develop individualized therapy. Different women will receive different treatments, based on specific characteristics of different tumors. “We need to match individual cancers with specific therapies and to bring personalized cancer treatment to the clinic, where it can save lives,” Gray says. Already, there are a few targeted drugs aimed at abnormalities found in some breast tumors, but not others. But the available drugs are only the tip of the iceberg of what might one day become available to target specific abnormalities in breast cancer. Some types of breast cancer have been particularly unresponsive to current targeted therapies, and the Dream Team aims to remedy that state of affairs. New treatments will be developed, and knowledge gained through research also will be used to deploy existing treatments more effectively, tailoring drug therapy to the individual. The focus of the studies will be on preclinical and clinical investigation of three breast cancer subtypes. These include estrogen receptor-positive breast cancers and HER2-positive breast cancers, for which some targeted therapies already exist. The third subtype is called triple-negative breast cancer because it exhibits no excess of those two markers or of a third marker, called the progesterone receptor. Triple-negative breast cancer often is not detected until it has spread and become life-threatening. It disproportionately affects young women and ethnic minorities. The Dream Team aims to learn more about how these tumors arise, how they grow, how they invade tissues far beyond their point of origin and how they become resistant to existing therapy. To an unusual degree, it is expected that other scientists and physicians will have access to the team’s cutting-edge discoveries and expertise through the development of a powerful and reliable informatics system. For example, results of the laboratory-conducted molecular profiling of a tumor could be sent electronically to a secure cancer genomics database. Dream Team members could analyze the profile, using the latest tools and knowledge, and provide recommendations for treatment to the patient’s physician. In addition to Gray and Slamon, the principal investigators of the Breast Cancer Dream Team are Arul Chinnaiyan, MD, PhD, of the University of Michigan; David Haussler, PhD, of UC Santa Cruz; Peter Sorger, PhD, of Harvard Medical School; Terence Speed, PhD, of UC Berkeley; Zena Werb, PhD, of UCSF; Alan Ashworth, PhD, of the Institute of Cancer Research, UK; Joan Brugge, PhD, of Harvard Medical School; Gregory Hannon, PhD, of Cold Spring Harbor Laboratory; Craig Jordan, PhD, DSc, of Fox Chase Cancer Center; Kent Osborne, MD, of Baylor College of Medicine; and Max Wicha, MD, of the University of Michigan Comprehensive Cancer Center. Dan Krotz from the Communications Department of the Lawrence Berkeley National Laboratory provided information contained in this article.

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