Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


New technique helps scientists reveal interactions between genes and drugs


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:

More articles from Life Sciences:

nachricht Make way for the mini flying machines
21.03.2018 | American Chemical Society

nachricht New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

TRAPPIST-1 planets provide clues to the nature of habitable worlds

21.03.2018 | Physics and Astronomy

The search for dark matter widens

21.03.2018 | Materials Sciences

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>