'Magic Shotgun' May Be Best Treatment For Cancer

'Magic Shotgun' May Be Best Treatment For Cancer

Written by Alex Reid
Posted June 18, 2012

The 'magic bullet' in the pharmacological world describes chemicals that specifically attack one gene or protein involved in a particular part of a disease process.

The German scientist Paul Ehrlich, considered the father of chemotherapy, originally coined the term ‘magic bullet’ to refer to the chemicals that could cure syphilis.

Researchers at the University of California, San Francisco (UCSF) and Mt. Sinai, New York, have taken this magic bullet approach and expanded it to create what they are calling a ‘magic shotgun,’ reports ScienceDaily.

The magic shotguns sift through the known universe of chemicals to find the few special molecules that broadly disrupt the whole diseases process.

Drug design is all about disruption in the body. 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.

While certain tissues and areas need to be disrupted, unwanted interactions with other molecules in the body occur. This refers to the toxicity of a drug.

Scientists use a therapeutic index to measure the ratio of effective dose to toxic dose of a drug. This allows them to define how severe the side effects of a drug will 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. However, most cancer drugs have a therapeutic index of 1, meaning the amount of the drug you need to take to treat the cancer is the exact amount that causes severe side effects.

But the new magic shotgun approach promises to help identify future drugs to fight cancer and other diseases that will be more effective and have fewer side effects.

“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."

In the June issue of the journal Nature, the magic shotgun approach has already yielded two potential drugs, called AD80 and AD81.

In studying fruit flies, these two drugs 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.

According to the National Cancer Society, about 1,638,910 new cancer cases are expected to be diagnosed in 2012. With numbers like this, minimizing the toxicity of cancer drugs is a big goal for many pharmaceutical companies. Shokat and his colleagues believe that the shotgun approach is one way to do this.

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