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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>