miércoles, 17 de octubre de 2012

Basser Research Center: Focusing on BRCA-Related Cancers ▲ NCI Cancer Bulletin for October 16, 2012 - National Cancer Institute

NCI Cancer Bulletin for October 16, 2012 - National Cancer Institute

Basser Research Center: Focusing on BRCA-Related Cancers

Cancer Centers iconThe recently opened Basser Research Center for BRCA Exit Disclaimer has a unique mission. As the name suggests, the center focuses solely on BRCA-related cancers, from basic research to clinical treatment. Located at the NCI-designated Abramson Cancer Center at the University of Pennsylvania (Penn) in Philadelphia, the center was funded with an initial donation of $25 million from Mindy and Jon Gray in honor of Mindy’s sister, Faith Basser, who died of ovarian cancer at the age of 44.
Dr. Susan Domchek, executive director of the Basser Research Center (Courtesy of Penn Medicine)
Dr. Susan Domchek hopes that research done at the Basser Research Center will eventually provide better options for people with BRCA mutations. (Courtesy of Penn Medicine)
People with BRCA gene mutations are at higher risk than the general population for developing several kinds of cancer, particularly breast and ovarian cancer. (See the box below.) Researchers at the Basser Center aim to develop ways to prevent BRCA-related cancers or detect them early. And investigators at the new center believe much of the research will have broader implications.
“What we will learn about BRCA1/2 in terms of risk, prevention, detection, and therapeutics can be applied not only to other forms of breast and ovarian cancers, but to other cancers as well,” said Dr. Susan Domchek, executive director of the center. “This is about understanding how cancers develop in these individuals, and, therefore, how we can target them.”
Breadth and Depth
One of the Basser Research Center’s strengths is that it draws on Penn’s clinical and research resources. For example, women with breast and gynecologic cancers receive treatment at facilities that specialize in those cancers and genetic counseling at a center that specializes in evaluating risk for women’s cancers. On the research side, the Basser Center draws on ovarian and breast cancer research programs, a translational research program, a center for personalized diagnostics, and a cell and vaccine production facility.
“The important thing is that this center has breadth and depth,” said Dr. Domchek. “The basic biology is as important as how a woman can talk to her 14-year-old about why she is having a bilateral mastectomy.”
By bringing together experts in immunotherapy, cancer genetics, molecular imaging, epidemiology, statistics, basic science, and clinical care, the Basser Research Center hopes to spur innovation, according to Dr. Chi Van Dang, director of the Abramson Cancer Center, which is funded in part by NCI.
“We have monthly meetings where all investigators present their work, and it really allows us to feed off each other,” explained Dr. Domchek. Especially valuable, she noted, is that clinicians and basic scientists interact regularly, allowing clinicians to bring their questions directly to the scientists.
Many of the researchers have worked together before, Dr. Dang noted, but the creation of the center is really a “superglue” that brings people together.
Delving Deeper
The funding infusion from the Gray family has allowed researchers to dive more deeply into existing research areas. For example, Penn has a tumor tissue and biospecimen bank, and the new funding will help establish a section of the biobank for serum and plasma specimens, which will be used to develop and test biomarkers.
What we will learn about BRCA 1/2 in terms of risk, prevention, detection, and therapeutics can be applied not only to other forms of breast and ovarian cancers, but to other cancers as well.

—Dr. Susan Domchek
“Early detection aided by biomarkers or imaging is incredibly important for us,” stressed Dr. Domchek. Currently, no effective screening method exists for ovarian cancer, and the most common method of prevention is removal of the ovaries, sometimes at a relatively young age. And many women who have BRCA1/2 mutations also have a bilateral mastectomy to reduce their risk of developing breast cancer.
The funding has also enabled Basser researchers to delve into other new areas, such as new imaging capabilities and immune-based treatment strategies.
“Some of our researchers are studying specific molecular targets that will allow us to develop imaging agents [for] early detection of disease,” explained Dr. Dang. “On the flip side, the same [molecules] might be targeted directly with immune cells that we can engineer. Ultimately, we want to develop vaccines and imaging techniques that will allow women [to forgo] those surgeries in the future,” he said.
Although the proteins produced by BRCA1/2 are known to play a critical role in repairing damaged DNA, scientists do not yet fully understand how BRCA mutations can cause cancer or why mutations in certain regions of the genes appear to raise the risk of developing ovarian cancer rather than breast cancer, said Dr. Dang. Such an understanding would help researchers find ways to prevent and treat these cancers, noted Dr. Domchek.
When to Test?
Dr. Chi Van Dang, director of the Abramson Cancer Center (Courtesy of Penn Medicine)
Dr. Chi Van Dang believes that research being done at the Basser Center may lead to better imaging techniques and immunotherapies. (Courtesy of Penn Medicine)
The Basser Research Center is also using funds from the Gray's donation to improve outreach, education, and collaboration. This includes partnering with an organization called Facing Our Risk of Cancer Empowered (FORCE), an advocacy and support group for people affected by hereditary breast and ovarian cancer. The center has also created a webpage Exit Disclaimer where people can request clinical or research information about BRCA-related cancers and has hired more genetic counselors who can help people find local resources or join a clinical trial.
Just the process of testing for BRCA mutations is fraught with difficult questions, Dr. Dang noted.
“At what age do you test, when do you inform patients of the results, what is the impact of those results, and how might the results affect the individual’s psychological outcome,” he said. “This research is not molecularly based, but it’s extremely important for the mental and physical health of individuals.”
In part because the Basser Center is spurring collaboration and innovation, and allowing researchers to dig more deeply into their projects, he hopes the findings will come more quickly. “Instead of coming out in 3 to 5 years, we’ll be seeing information in a shorter timeframe,” he predicted.
The funding will allow Basser researchers to do many new things, but “the most important thing that I’ve seen to date is that [the new center] really brings hope to people with these mutations,” said Dr. Dang.
—Virginia Hulme
As an NCI-designated comprehensive cancer center, the Abramson Cancer Center is funded in part by a Cancer Center Support Grant (P30CA016520).
Further reading: “BRCA1 and BRCA2: Cancer Risk and Genetic Testing
When BRCA1 and BRCA2 work normally, the proteins they produce suppress tumor formation by helping to prevent uncontrolled cell growth. Sometimes, however, these genes contain harmful mutations that increase the risk of certain cancers. Women with mutations in BRCA1 or BRCA2 have greater risks of breast and ovarian cancers, as well as cervical, uterine, pancreatic, colon, stomach, gallbladder and bile duct cancers, and melanoma. Men with these mutations have a higher risk of breast, pancreatic, prostate, and testicular cancers.
Women with BRCA gene mutations are five times more likely to develop breast cancer than women without a mutation. Hereditary BRCA mutations account for about 5 to 10 percent of all breast cancers and 10 to 15 percent of all ovarian cancers among white women in the United States.
People whose family history suggests that they may have a harmful BRCA gene mutation can undergo genetic testing.
People with a harmful BRCA mutation have several options that may help reduce their risk of developing cancer: screening and other forms of surveillance; surgery to remove at-risk tissue; behavioral changes, such as losing weight and increasing physical activity; and taking drugs that have been shown to reduce the risk of breast cancer.

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