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 On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

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: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>