Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Technique Reveals Drug Resistance in Breast Cancer Tumors

12.12.2002


Could Spare Half of Women From Chemotherapy

Oncologists at the Duke Comprehensive Cancer Center are testing a new technique called gene expression profiling that subtypes each breast cancer tumor by its genetic defects so that doctors can tailor their treatment to inhibit that particular tumor.

The researchers believe the technique could spare millions of women from needlessly receiving toxic chemotherapy, and they are leading a national clinical trial to study gene profiling.



“Currently, we have no predictive model to determine who will respond to hormonal therapies and who won’t, so we prescribe chemotherapy as a backup measure to ensure the cancer’s demise,” said Matthew Ellis, M.D., Ph.D., director of the breast cancer program at Duke. “This one-treatment-fits-all approach leads to a huge amount of over treatment, with up to 50 percent of women unnecessarily receiving chemotherapy.”

The new technique uses a commercially available gene chip to create a genetic “fingerprint” of each tumor. Doctors use the chip to categorize each tumor by its genetic defects and predict whether the tumor will respond to standard hormonal therapies or whether it will require additional chemotherapy, said Ellis.

“The gene chip allows us to measure levels of various genes that give rise to drug resistance, so we can paint a picture of what a responding cancer cell looks like and what an unresponsive cell looks like,” said Ellis. “With such fingerprints, we can develop new drugs that target the cellular signaling pathways that have malfunctioned.”

Ellis will present his study design at the 25th annual San Antonio Breast Cancer Symposium Dec. 11-14. The multi-center study of 140 women is funded by a $3.7 million grant from the Avon Foundation and the National Cancer Institute.

Participants in the study will provide biopsies of their tumors, then receive the estrogen-depriving drug letrozole before surgery to shrink their cancers. Letrozole reduces the production of estrogen that fuels the growth of up to 80 percent of all breast cancers. Yet inexplicably, some tumors that are expected to respond to hormonal therapies remain unaffected by treatment. And, some tumors that initially respond to anti-estrogen drugs later become resistant. Doctors have long wondered what drives these paradoxical effects, but answers have been slow in coming.

To illuminate the answers, Ellis’ team will use gene expression profiling to measure subtle changes in 16,000 genes as they react, or fail to react, to Letrozole. “We are trying to identify the cellular programs that must be engaged or shut off for aromatase inhibitors to be successful,” said Ellis. Aromatase inhibitors block an enzyme called aromatase, which converts the male hormone androgen into the female hormone estrogen. Thus, women taking letrozole make almost no estrogen.

Gene expression profiling works like this: scientists use a gene chip to measure the activity of thousands of genes that drive a tumor’s reaction to treatment. A gene’s activity is measured by how many copies of messenger RNA (mRNA) it produces. They extract the mRNA from a cell, label it with fluorescent tags, and inject the mixture onto fingernail-sized gene chips. The mRNA binds to its complementary probe on the chip.

Afterward, scientists shine a special light on the chip. They can tell by the intensity of light how much messenger RNA -- and hence, copies of each gene -- is present on the chip. Thus, the researchers obtain the gene expression profile of the activity of thousands of genes. If one gene shows low activity, or another is overactive, therein lays the culprit, said Ellis.

“We used to think that hormonal therapies simply shut off cell growth, but it’s much more complicated than that,” said Ellis. “Hormonal drugs affect the entire estrogen pathway -- many more genes than we ever realized -- including those that regulate cell proliferation, cell survival, tissue invasion, metastasis and angiogenesis.” Metastasis is the spread of a cancer beyond its initial tumor, and angiogenesis is the process of blood vessel growth by which a tumor nourishes itself.

Ellis said that estrogen receptors -- small molecular docking stations in the nucleus of cells -- appear to be defective in some tumor cells. The receptors may be disconnected from tumor cell growth, or they have become super-sensitized to estrogen so that even tiny amounts can make the tumor grow. In the latter case, even an aromatase inhibitor would not completely prevent estrogen from reaching the receptor and allowing the tumor to grow.

Indeed, it is not uncommon for estrogen super-sensitive tumors to continue growing when deprived of most of their estrogen, said Ellis. Such a phenomenon is but one of the perplexing clinical questions they hope to answer.

“The value in gene expression profiling is that we can subtype each breast cancer, then tailor treatments to target that specific tumor’s defects,” said Ellis. “This would allow us to know when we should use hormonal therapies, when we should add chemotherapy, and to determine which drugs to develop to target hormonal therapy resistance.”

Other centers participating in the clinical trial include University of California San Francisco, University of North Carolina Chapel Hill and the Dana Farber Cancer Institute.

contact sources :
Dr. Matthew Ellis , (919) 668-0718
ellis053@mc.duke.edu

Rebecca Levine | EurekAlert!
Further information:
http://dukemednews.org/news/article.php?id=6180
http://cancer.duke.edu/

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

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: LZH showcases laser material processing of tomorrow at the LASYS 2018

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...

Im Focus: Self-illuminating pixels for a new display generation

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...

Im Focus: Explanation for puzzling quantum oscillations has been found

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...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

Magnesium magnificent for plasmonic applications

23.05.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>