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 Periodic ventilation keeps more pollen out than tilted-open windows
29.03.2017 | Technische Universität München

nachricht Improving memory with magnets
28.03.2017 | McGill University

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: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Periodic ventilation keeps more pollen out than tilted-open windows

29.03.2017 | Health and Medicine

Researchers discover dust plays prominent role in nutrients of mountain forest ecoystems

29.03.2017 | Earth Sciences

OLED production facility from a single source

29.03.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>