U-M’s Cancer Dream Team

Targeting better treatments for breast cancer

There are dream teams in basketball and dream teams in business, but you don’t hear much about them in the sedate world of academia. So, it was a surprise when Cancer Center researchers Max Wicha, M.D., and Arul Chinnaiyan, M.D., Ph.D., learned they were part of a national “dream team” of biomedical research scientists selected to receive an $18 million grant from a charitable initiative called Stand Up To Cancer.

It was even more unusual to see the dream team awards announced May 27 in a national media blitz that featured prime-time coverage on ABC, CBS and NBC. But then, nearly everything about Stand Up to Cancer, or SU2C, is out of the ordinary.

The organization was started in 2007 by six women in the media and entertainment industries whose lives were affected by cancer. Most of the $73.6 million in research funding awarded by SU2C to five teams of cancer researchers was donated on September 5, 2008, during a celebrity-studded fund-raising event broadcast live by all three major TV networks.

SU2C’s fund-raising methods may be unconventional, but the scientists being funded are among the best in the country. Wicha and Chinnaiyan will work with 11 other researchers from major U.S. medical schools and cancer centers. They will focus on finding molecular differences among the three major subtypes of breast cancer, especially those that help the cancer become resistant to treatment over time. The team’s goal is to develop targeted therapies that will be less toxic and more effective, because they are designed to attack the specific genes or signaling pathways active in each type of breast cancer.

One fundamental mechanism the team will study is the role of cancer stem cells — small populations of cancer cells believed to be responsible for the growth and spread of breast tumors.

“The goal of current therapies has been to kill as many cancer cells as possible,” says Wicha, Distinguished Professor of Oncology, director of the U-M Comprehensive Cancer Center and one of several U-M scientists who discovered cancer stem cells in breast tumors. “The current model may lead to treatments that are limited in their effectiveness, because they are not targeted at cancer stem cells, which are resistant to existing therapies.”

Chinnaiyan, the S.P. Hicks Endowed Professor of Pathology, professor of urology and director of the Michigan Center for Translational Pathology, will be responsible for another important component of the SU2C study — creating a Web-based database to integrate existing molecular information about breast cancer. Having all the relevant information available in one searchable database will help researchers select and evaluate new drug combinations and breast cancer targets for future clinical trials.

“We’ve made significant progress in our understanding of the molecular basis of cancer,” adds Chinnaiyan. “Now, we need to bring this knowledge to clinicians, so we can move beyond a one-size-fits-all approach to cancer treatment.”
—SALLY POBOJEWSKI

For more information on the SU2C "Dream Team" grants
For patient information on breast cancer

Toxic Trigger

Too much acetaminophen can be too much of a good thing. Acetaminophen overdose is the leading cause of acute liver failure in the U.S., but the amount required to damage the liver and trigger a dangerous inflammatory response varies widely. What makes some people more sensitive to the drug than others?

Researchers in the Comprehensive Cancer Center studied mice to find clues to the mechanism of the drug’s toxicity. They discovered a signaling pathway that protected mice against the immune response triggered by acetaminophen-induced liver damage. If proteins in the pathway were missing, an overdose of the drug caused death within a few hours. Understanding how these cellular signals work could lead to new treatments for liver failure and other types of tissue damage. The notion has broad implications for host response to cancer, of which cellular damage of the same sort, necrosis, is a hallmark.
—SP

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Rat Tales

When placed in a new environment, high-anxiety rats tend to cower in the dark, while their low-anxiety companions explore bright, open spaces. Scientists at the Molecular and Behavioral Neuroscience Institute found that these behavioral differences were linked to a brain chemical called fibroblast growth factor 2. Rats that were genetically prone to high anxiety had lower levels of FGF2 and fewer new brain cells in the hippocampus than low-anxiety rats.

Providing enriched living quarters or direct FGF2 supplements increased production of FGF2 in high-anxiety rats, decreased their anxious behavior, and increased production of adult stem cells in the hippocampus. U-M scientists also found that FGF2 is decreased in the brains of depressed humans, so they believe FGF2 could be a promising target for drugs to treat human depression and anxiety disorders.
—SP

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Stroke Aftermath

New research by David J. Pinsky, M.D., the J. Griswold Ruth, M.D., and Margery Hopkins Ruth Professor of Internal Medicine, and a team of Cardiovascular Center researchers indicates that an enzyme called CD39 could be the key to preventing permanent brain damage after a stroke.

In previous research, Pinsky, who also is a director of the Cardiovascular Center, discovered CD39 on the surface of cells that line the inside of arteries and blood vessels where clots form. Now, his research team has shown that CD39 also is produced on the surface of white blood cells.

By studying mice that lacked the ability to make CD39, scientists discovered that the enzyme’s job is to mediate a delicate balancing act between signals that accelerate inflammation in damaged blood vessels and competing signals that suppress platelet activation and cool inflammation down. Pinsky says additional research to understand how CD39 works could someday lead to safer, more effective stroke treatments.
—SP

An expanded version of the story
Patient information on stroke prevention (PDF)