Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Combination treatment may improve survival of breast cancer patients with brain metastases

02.11.2012
Adding angiogenesis inhibitor to anti-HER2 treatment significantly extends survival in mouse model

Adding an angiogenesis inhibitor to treatment with a HER2-inhibiting drug could improve outcomes for patients with HER2-positive breast cancer who develop brain metastases. In their report published online in PNAS Plus, Massachusetts General Hospital (MGH) investigators report the first preclinical study combining antiangiogenic and anti-HER2 drugs in an animal model of brain metastatic breast cancer.

"We have shown dramatic improvement in survival by slowing the growth of brain metastatic, HER2-amplified breast cancer," says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH, Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School and senior author of the study. "This is particularly important because patients with this type of breast cancer have an increased risk of brain metastases, which have not responded to current therapies."

A quarter of breast cancers are driven by overexpression of the growth factor HER2, making them particularly aggressive. Treatment with drugs that block the pathway controlled by HER2 – trastuzumab (Herceptin) and lapatinib (Tykerb) – suppresses the growth of these tumors and extends patient survival. But these patients are at increased risk of developing brain metastases, which have resisted anti-HER2 treatment. Angiogenesis is also known to have an important role in breast cancer, and although previous studies combining chemotherapy with the antiangiogenesis drug bevacizumab (Avastin) delayed disease progression, they have not extended overall survival.

In addition to directly blocking the HER2-controlled growth pathway, anti-HER2 drugs also contribute to suppression of tumor-associated blood vessels. Previous studies in Jain's lab suggested that the proangiogenic factor VEGF may overcome the antiangiogenic effects of anti-HER2 drugs. This observation led the researchers to investigate whether blocking the VEGF pathway would improve the results of anti-HER2 treatment. Their study used a new mouse model in which the proliferation of HER2-amplified breast cancer cells implanted into brain tissue could be monitored over time. The researchers first confirmed that, as in human patients, treatment with a single anti-HER2 drug suppressed tumor growth in breast tissue but not within the brain.

While treatment with DC101, an antibody that blocks the VEGF pathway in mice, improved survival compared with either anti-HER2 drug, combining DC101 with one anti-HER2 drugs produced even greater survival improvement, including the death of tumor cells through significant reduction in tumor-associated angiogenesis. A triple combination of DC101 with both anti-HER2 drugs had the most dramatic effects. Animals receiving a single anti-HER2 drug along with DC101 lived more than three times as long as control animals, while those receiving all three drugs lived five times as long.

Jeffrey Engelman, MD, PhD, of the MGH Cancer Center, co-corresponding author of the PNAS Plus report, notes that a clinical trial now underway combining chemotherapy with bevacizumab in breast cancer addsanti-HER2 treatment for those participants whose tumors are HER2-amplified. The results of the current MGH study suggest that investigating a triple combination may be particularly beneficial. "With targeted therapies like anti-HER2 drugs suppressing the growth of tumors outside the central nervous system, brain metastasis is becoming a more common cause of treatment failure."

Co-corresponding author Dai Fukumura, MD, PhD, of the Steele Lab adds, "A clinical trial of this sort of triple combination will be an important next step. And in the meantime, we will continue to investigate the mechanisms of resistance to the effects of both double and triple combinations." Fukumura is an associate professor of Radiation Oncology and Engelman an associate professor of Medicine at Harvard Medical School.

Co-lead authors of the PNAS Plus article are David Kodack, PhD, Euiheon Chung and Hiroshi Yamashita of the Steele Lab. Additional co-author are Joao Incio, MD, Annique Duyverman, Yuhui Huang, PhD, Eleanor Ager, PhD, Walid Kamoun, Shom Goel, MBBS, Matija Snuderl, MD, Alisha Lussiez, Lotte Hiddingh and Sidra Mahmood, Steele Lab; Youngchul Song and April Eichler, MD, MGH Cancer Center; Christian Farrar, PhD, MGH Martinos Center for Biomedical Imaging, and Bakhos Tannous, PhD, MGH Neurology. Support for the study includes grants from the National Cancer Institute and a Breast Cancer Research Innovator Award from the Department of Defense

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."

Sue McGreevey | EurekAlert!
Further information:
http://www.massgeneral.org/

More articles from Health and Medicine:

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

nachricht Prospect for more effective treatment of nerve pain
20.02.2017 | Universität Zürich

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>