Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New technique helps scientists reveal interactions between genes and drugs

03.08.2004


Scientists have developed a new screening technique to help them look for genes that change patients’ responses to cancer drugs and other medications.

Researchers looking for such connections confront an enormous hunting ground of approximately 33,000 human genes. Normally their only options for mounting a search in such a vast field are either to rely on anecdotal reports of dramatically altered patient reactions, or to conduct extensive surveys of the genes for all the proteins known to interact with a given drug.

The new approach lets nature and a robotic screening system do the majority of the hunting for them. In their initial test, which will be described in the August 10 Proceedings of the National Academy of Sciences, investigators rapidly found potential connections between two chemotherapy drugs and two regions of human DNA that contain approximately 100 genes each. The study is currently available online.



"This isn’t the answer to everything in terms of finding these links, but it’s an important breakthrough," says senior investigator Howard L. McLeod, PharmD., associate professor of medicine, genetics and of molecular biology and pharmacology. "This approach is very likely to allow us to find links between pharmaceuticals and genes that we never would have been able to anticipate."

McLeod is an expert in pharmacogenetics, a new field where scientists are learning that a person’s genes can dramatically influence the effectiveness of medications. These differences can change a drug that is a lifesaver for some patients into a toxin for others, or influence whether a medication provides little benefit or is a remarkably effective treatment. By identifying genetic factors that affect patients’ responses to drugs, scientists hope someday to enable clinicians to customize treatment plans.

McLeod and colleagues in the Division of Biostatistics took advantage of cell lines established as part of the effort to map the human genome. Researchers at the Centre d’Etude du Polymorphisme Humain in Paris, France have created approximately 700 human cell lines from multiple generations of large families in Utah, France and elsewhere.

Washington University scientists exposed cells from more than 400 of the lines to varying doses of two chemotherapy drugs, 5-fluorouracil and docetaxel. The cells were non-cancerous, but chemotherapy can kill both cancerous and non-cancerous cells. Chemotherapy is given as a treatment for cancer because cancer cells are generally more sensitive to its effects, but many factors, including the genetics of the cells’ non-cancerous precursors, can influence that sensitivity.

Scientists used a robotic screening system to look for cell lines with increased sensitivity to the drugs, demonstrated by higher numbers of cell deaths in response to low drug doses. The robot also highlighted cell lines with high resistance to the drugs where few or no cells were killed.

In the future, patients whose cells are particularly sensitive to chemotherapy may be able to be treated with relatively low doses, reducing side effects. Patients whose cells are particularly resistant may need special or added medications to assure a good outcome.

Scientists already know a great deal about inheritance of genetic markers among the cell lines. This enabled Washington University researchers to compare and contrast the genetics of a cell line with altered sensitivity to cell lines from other family members and from multiple generations of the same family. Children get a random mixture of genes from both parents, so both genetic markers and changes in sensitivity are sometimes passed from parent to child and sometimes aren’t. When a particular genetic marker is consistently passed from parent to child at the same time as a change in sensitivity, that tells scientists they need to look near the marker for a gene that changes sensitivity.

The initial test of the new approach found connections between increased sensitivity to the drugs and areas on chromosomes 5 and 9.

"That part of chromosome 9 turned up in an earlier search we conducted for these genes," McLeod says. "Lightning’s struck twice there now, so we’re definitely going to be looking for a gene that affects sensitivity in this region."

McLeod’s group already has applied the new screening technique to six more cancer drugs, but he says they’ve just begun to find ways to use the new approach.

"This is not a cancer research technique, it’s a drug research technique," says James W. Watters, Ph.D., lead author of the study and instructor of medicine. "We want to find ways to look at new endpoints -- for example, how thoroughly does a drug hit its target of interest, or how much can it slow growth or other cellular processes? Then we’ll be able to look at genetic effects on medications for a range of disorders."

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>