Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New cancer drug screening technique more closely mirrors reality

15.03.2010
Improving on traditional screening tests for potential anti-cancer drugs, scientists at Dana-Farber Cancer Institute have developed a laboratory technique that more closely simulates the real-world conditions in which tumor cells mingle with the body's normal cells.

Because these neighboring cells – key components of what is known as the "tumor microenvironment" – can alter the effectiveness of anti-cancer drugs, the new technique may help researchers narrow the field of possible therapies more quickly and identify the most promising candidates more readily.

The technique, described in a study published online today by the journal Nature Medicine, can be used to study a wide variety of cancer cells that infiltrate an equally wide range of normal tissues, the authors say.

"Despite their often impressive results in the laboratory, for every 100 potential anti-cancer therapies administered in patients in clinical trials, only about eight prove safe and effective enough to receive Food and Drug Administration approval," says the study's senior author, Constantine Mitsiades, MD, PhD, of Dana-Farber. "This success rate is clearly not as high as we would like it to be, and one reason may be that so far we haven't had a good way to account, at the earliest stages of laboratory testing, for the impact of the tumor microenvironment on these drugs."

In conventional drug screenings, different types of cancer cells are exposed to hundreds or thousands of compounds under laboratory conditions in which only tumor cells are present. The compounds that prove best at killing tumor cells are then earmarked for further study.

A shortcoming of this approach, Mitsiades says, is that "in the human body, tumor cells don't grow in isolation, but come in contact with a wide variety of non-malignant cells. Many of these 'accessory' cells support one another through direct contact or by producing substances known as growth factors. Tumor cells can take advantage of these signals to fuel their own growth."

Evidence from a variety of studies suggests that these otherwise normal elements of the tumor microenvironment can impede the effectiveness of anti-cancer drugs and allow cancer to become resistant to different therapies – one of the biggest challenges in oncology.

To get a better understanding of this phenomenon and develop treatments to address it, Mitsiades and his colleagues developed a technique in which tumor and normal cells are "co-cultured" – that is, grown together – and exposed to hundreds or thousands of compounds in large-scale screening tests. In the technique, dubbed "cell-specific in vitro bioluminescence imaging," or CS-BLI, the cancer cells in each sample are equipped with a gene that makes them glow – a process unaffected by the normal cells nearby. By measuring the amount of light emitted by each sample after treatment, investigators can determine which compounds are most proficient at killing tumor cells, and whether this effectiveness changes when normal cells are around the tumor. (To make sure the candidate drugs aren't also killing normal cells, researchers can do a "counter-screen," in which they measure the effect of each compound on the normal cells.)

While there are other techniques for screening drug activity in co-cultures of malignant and normal cells, they either involve radioactivity or entail a time-consuming process of data capture and analysis, rendering them too cumbersome for large-scale studies, Mitsiades remarks.

With CS-BLI, Mitsiades and his colleagues have identified numerous compounds that acted powerfully against isolated samples of tumor cells but were significantly less effective against the same types of tumor cells co-cultured with non-malignant cells. Perhaps surprisingly, they also identified some compounds which are more effective against tumor cells mixed with non-malignant cells than against tumor cells alone.

In this latter category, researchers found a particular compound that was more active against myeloma tumor cells, both in laboratory cultures and mice, when the cells were in contact with healthy cells of the bone marrow – their usual location in patients. The compound also prevented the myeloma cells from responding to growth signals produced by the bone marrow cells. With conventional techniques, candidate drugs such as this one would have gone completely unnoticed, Mitsiades observes.

He emphasizes that CS-BLI is not a technique for predicting which anti-cancer agents will be effective in individual patients, but can help researchers identify which agents are the best prospects for additional investigation.

"It will be of use in prioritizing candidate drugs for further rigorous study of their properties before embarking on clinical trials," he remarks. "This technique may show that the classical methods of studying candidate cancer drugs in laboratory conditions have overestimated the effectiveness of some agents, and underestimated others.

"The technique also provides a powerful tool for determining which biological mechanisms allow cancers to become resistant to certain treatments and which new therapies can neutralize those mechanisms. Hopefully, combining such new therapies with other, established or investigational, treatments may contribute to improved success rates of clinical trials."

Funding for the study was provided by the Dunkin' Donuts Rising Stars program at Dana-Farber, the Chambers Medical Foundation, the Steven Cobb Foundation, and the National Institutes of Health.

The lead author of the study is Douglas McMillin, PhD, of Dana-Farber. Co-authors include Jake Delmore, Ellen Weisberg, PhD, Joseph Negri, D. Corey Geer, Steffen Klippel, PhD, Nicholas Mitsiades, MD, PhD, Robert Schlossman, MD, Nikhil Munshi, MD, Andrew Kung, MD, PhD, James Griffin, MD, Paul Richardson, MD, and Kenneth Anderson, MD, all of Dana-Farber.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

Teresa Herbert | EurekAlert!
Further information:
http://www.dfci.harvard.edu

More articles from Studies and Analyses:

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

All articles from Studies and Analyses >>>

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

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>