Local researcher records breast cancer breakthrough
Investigator finds key structure
A Buffalo researcher has determined the structure of a biochemical substance that leads to a majority of breast cancer tumors, a finding that could lead to more-effective therapies to treat and, perhaps, prevent the disease.
Breast cancer growth often depends on the presence of estrogens, the female sex hormones produced in the ovaries and other tissue. Estrogens attach to breast cancer cells, inducing them to grow out of control.
Aromatase is the key enzyme in the body that produces estrogens, and Debashis Ghosh and his colleagues at the Hauptman-Woodward Medical Research Institute finally cracked a problem that has eluded scientists for decades — what this important enzyme looks like in three dimensions.
“This is a dream come true,” Ghosh, the principal investigator, said after their work appeared in the latest edition of the journal Nature.
Enzymes help join or break apart substances in chemical processes.
Knowing the molecular structure of aromatase is significant, because researchers can design drugs specifically targeted to block its action instead of relying on medications produced through trial and error that also affect the entire body.
The thinking goes that drugs targeted to attach to aromatase and inhibit it, like a key made for one lock, will be more effective, longer-lasting, cause fewer side effects and open the door to preventing breast cancer.
“It’s an opportunity to design a new class of drugs,” said Ghosh, whose laboratory also determined the structure of the two other enzymes involved in controlling estrogen levels.
Breast cancer is the most common cancer among women in the United States and the second-leading cause of cancer death in women, after lung cancer. About 75 percent of women with breast cancer have tumors that contain estrogen receptors. This type of cancer depends on the female hormone to grow.
Hormone therapy is given to block the body’s naturally occurring estrogen and fight the cancer’s growth. Tamoxifen, for instance, is a common drug used today to block a tumor’s ability to use estrogen.
“Now that we know the structure of all three enzymes implicated in estrogen-dependent breast cancers, our goal is to have a personalized cocktail of inhibitors customized to the specific treatment needs of each patient,” Ghosh said.
In a commentary on the finding, Michael R. Waterman, chairman of biochemistry at Vanderbilt University School of Medicine, described the advance as vital for determining the complex and unique chemistry of aromatase.
“Perhaps more importantly, it provides a road map for future drug-discovery efforts in the battle against the most common form of breast cancer,” he wrote.
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