Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer’s Next Magic Bullet May Be Magic Shotgun

18.06.2012
Network Approach to Drug Design May Yield More Effective and Less Toxic Cancer Drugs, UCSF Study Suggests
A new approach to drug design, pioneered by a group of researchers at the University of California, San Francisco (UCSF) and Mt. Sinai, New York, promises to help identify future drugs to fight cancer and other diseases that will be more effective and have fewer side effects.

Rather than seeking to find magic bullets — chemicals that specifically attack one gene or protein involved in one particular part of a disease process — the new approach looks to find “magic shotguns” by sifting through the known universe of chemicals to find the few special molecules that broadly disrupt the whole diseases process.

“We’ve always been looking for magic bullets,” said Kevan Shokat, PhD, a Howard Hughes Medical Institute Investigator and chair of the Department of Cellular and Molecular Pharmacology at UCSF. “This is a magic shotgun — it doesn’t inhibit one target but a set of targets — and that gives us a much, much better ability to stop the cancer without causing as many side effects.”

Described in the June 7, 2012 issue of the journal Nature, the magic shotgun approach has already yielded two potential drugs, called AD80 and AD81, which in fruit flies were more effective and less toxic than the drug vandetanib, which was approved by the U.S. Food & Drug Administration last year for the treatment of a certain type of thyroid cancer.

Expanding the Targets to Lower a Drug’s Toxicity

Drug design is basically all about disruption. In any disease, there are numerous molecular interactions and other processes that take place within specific tissues, and in the broadest sense, most drugs are simply chemicals that interfere with the proteins and genes involved in those processes. The better a drug disrupts key parts of a disease process, the more effective it is.

The toxicity of a drug, on the other hand, refers to how it also disrupts other parts of the body’s system. Drugs always fall short of perfection in this sense, and all pharmaceuticals have some level of toxicity due to unwanted interactions the drugs have with other molecules in the body.

Scientists use something called the therapeutic index (the ratio of effective dose to toxic dose) as a way of defining how severe the side effects of a given drug would be. Many of the safest drugs on the market have therapeutic indexes that are 20 or higher — meaning that you would have to take 20 times the prescribed dose to suffer severe side effects.

Many cancer drugs, on the other hand, have a therapeutic index of 1. In other words, the amount of the drug you need to take to treat the cancer is the exact amount that causes severe side effects. The problem, said Shokat, comes down to the fact that cancer drug targets are so similar to normal human proteins that the drugs have widespread effects felt far outside the tumor.

While suffering the side effects of drugs is a reality that many people with cancer bravely face, finding ways of minimizing this toxicity is a big goal pharmaceutical companies would like to solve. Shokat and his colleagues believe the shotgun approach is one way to do this.

The dogma that the best drugs are the most selective could be wrong, he said, and for cancer a magic shotgun may be more effective than a magic bullet.

Looking at fruit flies, they found a way to screen compounds to find the few that best disrupt an entire network of interacting genes and proteins. Rather than judging a compound according to how well it inhibits a specific target, they judged as best the compounds that inhibited not only that specific target but disrupted other parts of the network while not interacting with other genes and proteins that would cause toxic side effects.

The article, “Chemical genetic discovery of targets and anti-targets for cancer polypharmacology” by Arvin C. Dar, Tirtha K. Das, Kevan M. Shokat and Ross Cagan appears in the June 7, 2012 issue of the journal Nature.

This work was supported by the American Cancer Society, The Waxman Foundation, and the National Institutes of Health—through grants R01CA109730, R01CA084309, R01EB001987 and P01 CA081403-11.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Jason Socrates Bardi | EurekAlert!
Further information:
http://www.ucsf.edu

Further reports about: Drug Delivery MAGIC Nature Immunology Shotgun UCSF bullet cancer drug disease process drugs magic bullets

More articles from Life Sciences:

nachricht Hidden dynamics detected in neuronal networks
23.07.2019 | Forschungszentrum Juelich

nachricht Towards a light driven molecular assembler
23.07.2019 | Christian-Albrechts-Universität zu Kiel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: MOF@SAW: Nanoquakes and molecular sponges for weighing and separating tiny masses

Augsburg chemists and physicists report how they have succeeded in the extremely difficult separation of hydrogen and deuterium in a gas mixture.

Thanks to the Surface Acoustic Wave (SAW) technology developed here and already widely used, the University of Augsburg is internationally recognized as the...

Im Focus: Better thermal conductivity by adjusting the arrangement of atoms

Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.

In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Hidden dynamics detected in neuronal networks

23.07.2019 | Life Sciences

Towards a light driven molecular assembler

23.07.2019 | Life Sciences

A torque on conventional magnetic wisdom

23.07.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>