Team Finds Breast Cancer Gene Linked to Disease Spread
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A team of researchers at Princeton University and The Cancer Institute of New Jersey has identified a long-sought gene that is fatefully switched on in 30 to 40 percent of all breast cancer patients, spreading the disease, resisting traditional chemotherapies and eventually leading to death.
The gene, called "Metadherin" or MTDH, is located in a small region of human chromosome 8 and appears to be crucial to cancer's spread or metastasis because it helps tumor cells stick tightly to blood vessels in distant organs. The gene also makes tumors more resistant to the powerful chemotherapeutic agents normally used to wipe out the deadly cells.
In identifying the genetic mechanism at play in the metastasis of breast cancer, the scientists may have answered one of the biggest mysteries in cancer research and paved the way for new drugs that could thwart the gene's diabolical actions.
"Inhibiting this gene in breast cancer patients will simultaneously achieve two important goals - reduce the chance of recurrence and, at the same time, decrease the risk of metastatic dissemination," said Yibin Kang, an assistant professor of molecular biology at Princeton, who led the research. "Clinically, these are the two major reasons why breast cancer patients die from the disease."
The work is described in the Jan. 6 edition of Cancer Cell.
The discovery is important for several other reasons, according to Michael Reiss, another author of the paper and director of the Breast Cancer Research Program at The Cancer Institute of New Jersey, a part of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.
"Not only has a new metastasis gene been identified, but this also is one of a few such genes for which the exact mode of action has been elucidated," said Reiss, also a professor of medicine, molecular genetics and microbiology at UMDNJ-Robert Wood Johnson Medical School. "That gives us a real shot at developing a drug that will inhibit metastasis."
The multidisciplinary research strategy used by the team to pinpoint the gene in breast cancer patients also could be used to find other genes involved in the spread of other cancers, scientists said.
"The potential health implications of this study are significant," Kang said.
The discovery is based on three years of work, using an approach that combines the emerging science of integrative genomics with the classical methods of clinical research and laboratory experiments.
"This paper is a great illustration of the way in which bioinformatics can be synergistically combined with experimental work to produce important results," said David Botstein, director of Princeton's Lewis-Sigler Institute for Integrative Genomics.
