Researchers at the Massachusetts General Hospital (MGH) Cancer Center have identified a subgroup of hard-to-treat breast cancers that may be sensitive to the drug cisplatin, rarely used in the treatment of breast tumors. They also have discovered the molecular basis of this sensitivity, which may help identify patients most likely to benefit from cisplatin treatment. The findings will be tested in a clinical trial anticipated to begin at the MGH Gillette Center for Breast Cancer and collaborating institutions later this spring.
"This paper describes a specific molecular pathway that makes these tumors sensitive to a therapy infrequently used for breast cancer," says Leif Ellisen, MD, PhD, of the MGH Cancer Center, senior author of the study to appear in the May 2007 Journal of Clinical Investigation and receiving early online release. "We’re excited that this work has led to the design of a clinical trial for women with a very difficult to treat form of breast cancer."
About two thirds of breast cancers contain receptor molecules for the hormones estrogen or progesterone, and in recent years antiestrogen drugs like tamoxifen have improved outcomes for women with those tumors. About 20 to 30 percent of tumors, some with hormone receptors, have elevated levels of a growth-promoting protein called HER2, and those tumors are candidates for treatment with the monoclonal antibody Herceptin. The third major subtype is the 15 to 20 percent of breast tumors that have neither estrogen nor progesterone receptors and also do not overexpress HER2.
Since these so-called "triple-negative" tumors are treatable with neither Herceptin nor antiestrogen drugs, the prognosis for patients with the tumors has been poor. Triple-negative tumors are the most common subtype found in patients with mutations in the BRCA1 gene, but they also appear in women without alterations in the so-called "breast cancer gene." There have been reports that BRCA1-associated, triple-negative tumors might be sensitive to cisplatin, a drug used to treat several other types of cancer, but whether the more common sporadic triple-negative tumors shared that sensitivity was unknown. The current study was designed to answer that question and to investigate the mechanism underlying cisplatin sensitivity.
The research team focused on the function of p63, a protein that plays a role in normal breast development and is related to the common tumor suppressor p53. They analyzed tissue samples from triple-negative breast tumors and normal breast tissues for the expression of several forms of p63 and another related protein called p73, known to promote the cell-death process called apoptosis.
The researchers found that a significant number of triple-negative tumors overexpress particular forms of p63 and p73, a pattern not seen in other types of breast cancers. Using an RNA interference system to inhibit the action of p63, they showed that the protein stimulates tumor growth by interfering with p73’s normal ability to induce cell death. Cisplatin was found to break up the binding of p63 to p73 and reactivate the cell-death process.
"The most important finding was that, if the tumor cells did not express both p63 and p73, the cells were not sensitive to cisplatin," says Ellisen. "These results suggest that testing p63 and p73 levels in patients’ tumors might help predict whether they would benefit from cisplatin therapy." Ellisen is an assistant professor of Medicine at Harvard Medical School.
The clinical trial to investigate the role of p63/p73 expression in determining cisplatin sensitivity will be led by MGH researchers through the Dana-Farber/Harvard Cancer Center. Starting in Boston in the coming weeks, the trial will be open to patient with advanced triple-negative breast cancer and eventually will be offered at other U.S. cancer research centers. Patients or physicians interested in the trial should call Karleen Habin at (617) 726-1922 and ask about the cisplatin trial for breast cancer.
Sue McGreevey | EurekAlert!
3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg
Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
22.05.2018 | Life Sciences
22.05.2018 | Earth Sciences
22.05.2018 | Trade Fair News