Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New test predicts blood cancer's sensitivity to experimental cancer drug

24.01.2007
Method identifies cancer cells that are 'primed' to die

A test developed by Dana-Farber Cancer Institute scientists is the first to identify which malignant blood cells are highly vulnerable to a promising type of experimental drugs that unleash pent-up "cell suicide" factors to destroy the cancer.

The researchers demonstrated that chronic lymphocytic leukemia, CLL, which is diagnosed in 10,000 Americans each year, is an easy mark for the new drug because the cancerous cells are strongly dependent on a particular survival molecule, Bcl-2, that keeps the self-destruct signals at bay. They showed that the investigational drug neutralizes the Bcl-2 action, unleashing molecules that trigger suicide in the cancer cells, a process known as programmed cell death or apoptosis.

The research in the laboratory of Anthony Letai, MD, PhD, of Dana-Farber, is described in the January issue of The Journal of Clinical Investigation. The lead author is Victoria Del Gaizo Moore, PhD, a member of the Letai group.

... more about:
»Bcl-2 »CLL »Letai »Molecule

Letai was a colleague of the late Stanley J. Korsmeyer, MD, of Dana-Farber, who discovered the key role in cancer played by anti-apoptosis molecules such as Bcl-2, which promote the survival of cells that are damaged or abnormal despite the body's efforts to eliminate them through apoptosis.

Inspired by this pioneering research, drug companies have begun testing novel Bcl-2 inhibiting drugs designed to restart the natural death processes thwarted by the survival molecule.

Letai said that his group has tested Abbott's investigational compound ABT-737 against cultured CLL cells with striking results. "We've treated CLL samples from several dozen patients, and each has responded to a very low concentration of the drug," said Letai. "We find it particularly interesting that the cells died within four hours."

Cells from CLL, a currently incurable disease, are vulnerable to this dramatic reversal of fortune because they are "primed for death;" they are surviving only because Bcl-2 proteins are blocking powerful cell-death molecular signals by holding them hostage. Primed cells, Letai explained, are like a car with a revved-up engine on the edge of a cliff, restrained only by its emergency brake; if the brake was released, the car would plunge over the cliff.

Drugs such as ABT-737, in effect, release the brake. The drug molecules liberate the pro-death signaling molecules from their Bcl-2 captors. These pro-apoptosis molecules -- a key one is called BIM -- then trigger a chain of events that cause the cell's power plants, or mitochondria, to rupture and spill out chemicals that cause the cell to die and be tagged for disposal. This class of drugs is expected to be relatively non-toxic to most normal cells, which are much less dependent on Bcl-2 function than are cancer cells to stay alive.

"It's essential to figure out which cancers are going to respond to the drug by identifying the cells that are dependent on Bcl-2 for survival," said Letai, who is also an assistant professor of medicine at Harvard Medical School. "Up to now there hasn't been a way to do this."

In developing the test, the Letai team first isolated mitochondria from cancer cells; then they exposed them to protein fragments – peptides – that were known to interact with survival molecules like Bcl-2. "If they interact, then the cell is primed to die, and the test will identify which of the survival molecules is keeping the cells alive," he added. "Then you know that to kill the cell, you have to target Bcl-2."

The researchers have dubbed the test "BH3 profiling" because the array of protein fragments are known as "BH3 domains." Letai said work is under way to make the laboratory profiling operation more automated, looking toward a time when it could be used on a routine basis to assess the vulnerability of patients' cancers to compounds that antagonize BCL-2 or related anti-death proteins.

"This is a totally new class of drugs and has the potential to be a major addition to how we treat cancer," he said.

Bill Schaller | EurekAlert!
Further information:
http://www.dfci.harvard.edu
http://www.dana-farber.org

Further reports about: Bcl-2 CLL Letai Molecule

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>