Information and Resources from the U-M Comprehensive Cancer Center

Research Roundup

First major gene mutation for hereditary prostate cancer risk discovered

After a 20-year quest to find a genetic driver for prostate cancer that strikes men at younger ages and runs in families, researchers have identified a rare, inherited mutation linked to a significantly higher risk of the disease.

Led by investigators at the University of Michigan Comprehensive Cancer Center and Johns Hopkins University School of Medicine, the study found that men who inherit this mutation have a 10 to 20 times higher risk of developing prostate cancer. Results appear in the New England Journal of Medicine.

While accounting for only a small fraction of all prostate cancer cases, the discovery may provide important clues about how this common cancer develops and help to identify a subset of men who might benefit from additional or earlier screening.

"This is the first major genetic variant associated with inherited prostate cancer," says study author Kathleen A. Cooney, M.D., chief of the division of hematology/oncology at the U-M Medical School.

The researchers used the latest technology to sequence the DNA of more than 200 genes. Researchers started with samples from the youngest patients with prostate cancer in 94 families who had participated in studies at U-M and Johns Hopkins. Each of those families had multiple cases of the disease among close relatives.

Members of four different families were found to have the same mutation in the HOXB13 gene, which plays an important role in the development of the prostate during the fetal stage and its function later in life. The mutation was carried by all 18 men with prostate cancer in these four families.

The researchers then found the HOXB13 gene mutation in 1.4 percent of a broader sample of 5,100 men treated for prostate cancer. Men with the mutation were much more likely to have at least one first-degree relative who also had been diagnosed with prostate cancer.

The researchers say with further study, it may be possible one day to have a genetic test for inherited prostate cancer in much the same way that tests are available to look for BRCA1 and BRCA2 mutations that greatly increase a womann's chance of developing breast or ovarian cancer. A genetic test for prostate cancer is not currently available.

Read the complete press release: Researchers find first major gene mutation associated with hereditary prostate cancer risk.

Avastin, Sutent increase breast cancer stem cells

Cancer treatments designed to block the growth of blood vessels were found to increase the number of cancer stem cells in breast tumors in mice, suggesting a possible explanation for why these drugs don't lead to longer survival, according to a study by researchers at the University of Michigan Comprehensive Cancer Center.

The drugs Avastin and Sutent have been looked at as potential breast cancer treatments. While they do shrink tumors and delay recurrence, the effect does not last, and the cancer eventually regrows and spreads.

"This study provides an explanation for the clinical trial results demonstrating that in women with breast cancer, anti-angiogenic agents such as Avastin delay the time to tumor recurrence but do not affect patient survival. If our results apply to the clinic, it suggests that in order to be effective, these agents will need to be combined with cancer stem cell inhibitors," says study author Max S. Wicha, M.D., director of the U-M Comprehensive Cancer Center.

The researchers treated mice with breast cancer using Avastin (bevacizumab) and Sutent (sunitinib), both of which work by stopping the growth and formation of blood vessels, a process called angiogenesis. The researchers found that tumors treated with these drugs developed more cancer stem cells, the small number of cells within a tumor that fuel a cancer's growth and spread and that are often resistant to standard treatment.

The U.S. Food and Drug Administration recently revoked approval of Avastin for treating breast cancer. The reversal was in response to clinical trials showing that the drug's benefit was short-lived, with breast cancer patients quickly relapsing and the cancer becoming more invasive and spreading farther throughout the body. Overall, the drug did not help patients live any longer.

The current study, published in the Proceedings of the National Academy of Sciences, suggests the possibility of combining anti-angiogenesis drugs with a cancer stem cell inhibitor to enhance the benefit of this treatment. The researchers are testing this approach in mice, and preliminary data looks promising. Clinical trials testing this research are not currently available.

Read the complete press release: Avastin, Sutent increase breast cancer stem cells, U-M study shows.

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