Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Tumor-fighting Ability in Popular Breast Cancer Drug

25.08.2004


For many patients with advanced breast cancer, the cancer drug Herceptin (trastuzumab) has offered new hope when traditional cancer drugs failed to work, shrinking tumors and sending some patients into remission.



Now Dihua Yu, M.D., Ph.D., and her colleagues at The University of Texas M. D. Anderson Cancer Center have uncovered a powerful new cancer-fighting property of Herceptin, an antibody-based drug that targets a protein on breast cancer cells called HER-2 (also called ErbB2). The discovery explains why some HER-2 positive patients don’t respond as well to the drug and also offers a potential solution that could allow more HER-2 positive patients to benefit from the treatment.

The study, which appears in the August 2004 issue of the journal Cancer Cell, demonstrates that the presence of a protein called PTEN in HER-2 positive patients’ tumor cells is a powerful predictor of who will respond to Herceptin. In normal cells, the PTEN protein helps control cell division, but in about half of breast tumors PTEN levels are very low or the protein is completely missing. Those PTEN-missing tumors did not respond to Herceptin treatment.


“Our goal is to allow doctors to quickly and accurately tailor cancer treatment to each individual patient,” says Yu, professor of surgical oncology, and the study’s principal investigator. “Tailored treatment means giving each patient the medication most likely to benefit her, while simultaneously minimizing side effects.”

In a recent clinical trial at M. D. Anderson, 65 percent of HER-2 positive patients taking Herceptin in addition to chemotherapy had a complete response rate, compared to 26 percent taking chemotherapy alone. But doctors have had no way to predict who among HER-2-positive patients, which account for about one-third of all breast cancer patients, is most likely to benefit.

“Previously, it was known that Herceptin binds to the HER-2 protein and causes it to degrade,” says Yu. “But this process takes days. What we found is that very quickly, within ten minutes of administration, Herceptin activates PTEN, a powerful tumor suppressor gene. We are adding a very new understanding of how Herceptin works.”

The scientists studied the tumors of 47 metastatic HER-2 positive breast cancer patients who had received Herceptin and chemotherapy as well as 37 patients who received chemotherapy alone. PTEN levels varied widely among both groups, but only 11 percent of patients who had a very low level of PTEN responded to Herceptin, versus 66 percent of those with high levels of PTEN. There was no correlation between PTEN level and response to traditional chemotherapy agents called taxanes.

“Our results show PTEN is a very powerful predictor of who will respond to Herceptin,” says Yu.

Breast cancer patients whose tumors make too much of the HER-2 protein are at much greater risk of metastasis because the HER-2 protein stimulates cells to grow and spread aggressively. When Herceptin attaches to the HER-2 protein, it interrupts those growth signals, which are sent through a series of signaling proteins inside the cell. PTEN acts as a natural brake on tumor growth by, among other things, blocking the effect of a growth promoting protein called PI3K.

Yu and her colleagues discovered that if they administered a drug that turns off PI3K in breast cancer cells in the laboratory, they became much more sensitive to the effects of Herceptin. The PI3K inhibitor mimicked the action of PTEN and restored the ability of Herceptin to slow or stop the growth of cancer cells.

Yu pointed out that there are several experimental PI3K inhibitors currently in clinical trials for treatment of breast cancer that, if they prove to be safe, could potentially be combined with Herceptin to boost its effectiveness in PTEN-missing breast cancers.

“In the past we looked for patients’ HER-2 expression, and if HER-2 was high we gave them Herceptin,” says Yu. “In the future, when patients come to M. D. Anderson we will look for patients with high levels of HER-2 and PTEN expression and these are the patients that we expect will benefit most from Herceptin. For those with low PTEN, we hope to be able to offer combination therapy with a PI3K inhibitor that might work synergistically to boost the effectiveness of Herceptin.”

Yu says she and her colleagues in the Breast Medical Oncology Department are planning a clinical trial to be conducted at M. D. Anderson in which they would test each patient for HER-2 and PTEN proteins and offer targeted treatment based on the level of each protein.

“There has been a need to develop new markers that can improve the efficacy of Herceptin,” says Francisco Esteva, M.D., Ph.D., an associate professor in the Department of Breast Medical Oncology. “This is one of the first studies that allows us to understand the mechanism of Herceptin resistance and offers a potential way to counteract it.”

“In the past, selecting a particular chemotherapy drug has been a lottery,” says Yu. “Patients had no way of knowing if they would benefit. The new generation of cancer drugs is providing targeted treatment with fewer side effects and giving patients a better chance that a particular treatment will work for them.”

The study was funded by grants from the National Institutes of Health and M. D. Anderson Cancer Center. Yu’s co-authors include Yoichi Nagata, M.D., Ph.D.; Keng-Hsueh Lan, M.D.; Xiaoyan Zhou; Ming Tan, M.D., Ph.D.; Esteva; Aysegul A. Sahin, M.D.; Kristine S. Klos, Ph.D.; Ping Li; Nina T. Nguyen; Gabriel N. Hortobagyi, M.D. and Mien-Chie Hung, Ph.D. of M. D. Anderson; and Brett P. Monia of ISIS Pharmaceuticals.

| newswise
Further information:
http://www.mdanderson.org

More articles from Health and Medicine:

nachricht Penn studies find promise for innovations in liquid biopsies
30.03.2017 | University of Pennsylvania School of Medicine

nachricht 'On-off switch' brings researchers a step closer to potential HIV vaccine
30.03.2017 | University of Nebraska-Lincoln

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

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>