Oncological Sciences Center

Nanopolymer tests effectiveness of cancer drugs

March 29, 2011

After being diagnosed with advanced prostate cancer about four years ago, Andrew Ehrmann decided not to surrender hope. So he is participating in his second clinical trial to test experimental drugs that might stave off his incurable disease. 

 

"Maybe it will work for me," the 50-year-old said. "You don't know if you'll respond to it at all ... otherwise you will wait to die, and that's depressing."

So Ehrmann is not only aware of the current efforts researchers are making when it comes to developing new cancer drugs, he is in favor of new approaches to developing safer and effective cancer treatments. "The more testing of a drug you can do before people start taking it, the better," he said. 

That is the idea behind a new nanopolymer that Purdue University researchers have developed. The nanopolymer, called pIMAGO, can be used to determine whether cancer drugs have been effective in treating the biochemical processes that lead to cancer cell formation. 

 

"It can potentially replace radioisotopes and special antibodies," said W. Andy Tao, an associate professor of biochemistry and analytical chemistry and co-creator of the nanopolymer. "So you don't need to wait for making antibodies, which takes quite a while for a regular lab." 

 

Tao's research was published online in the March edition of the journal Analytical Chemistry. 

 

The nanopolymer is an extremely tiny synthetic chemical compound. Polymers can be found in nature as with cellulose, a complex carbohydrate found in plant cell walls, or be developed in a lab similar to plastic. However, pIMAGO is a nanoscopic polymer, meaning that it is so small it cannot be seen by the human eye or microscope. 

 

This nanopolymer is also similar to a small synthetic protein because it is spherical and can easily be dissolved in water, said Anton Iliuk, a doctoral student in biochemistry at Purdue and first author of the study. 

 

So when added to a biological solution, nanopolymers attract and bond with proteins that have been modified by kinase, an enzyme that is known to cause cancer cell formation when overactive. The kinase normally adds phosphorous to the proteins but in cancer cells kinase activity is much more active and unregulated, explained Iliuk, who also helped develop pIMAGO. 

 

A cancer drug's effectiveness is then exposed by the solution color. A lightly colored solution indicates little kinase activity and shows that the drug was effective. But a darker solution indicates more kinase activity and a less effective drug.

 

Dr. Wael Harb, an oncologist with Indiana University Health Arnett, said these kinase inhibitors fall into a new generation of cancer drugs that are biologically targeted therapies, many of which he uses to treat some of his cancer patients. 

 

"This kinase (is) a large group of enzymes inside the cells but a lot of them are mutated or overactivated in cancer cells, which might be the culprit causing these cancer cells to grow without control," said Harb, who is also medical director of Horizon Oncology Center. 

 

So designer drugs block kinase activity. However, the difficult part of developing these drugs is screening for effectiveness. "You start with 1,000 drugs in the lab and you are lucky if you get one out of these 1,000 drugs to become part of the clinical trial system," Harb said. "So it's a very costly process and very time consuming." 

 

In his eyes, the pIMAGO nanopolymer research looks promising. 

 

"This is a very hot area of research," he said. "Many companies around the world are developing kinase inhibitors. There is a lot of resources spent on the testing of that. So any progress made in that area can benefit a lot of researchers around the world (who are) working on kinase inhibitors." 

 

Tao argues that his nanopolymer would be an easier and less expensive way to test these drugs. Current screening methods include using radioisotopes, which are potentially dangerous due to radiation exposure. Also, antibodies are used to screen kinase inhibitors. 

 

However, since antibodies are in short supply, this can an expensive endeavor, Tao said. 

 

Tao and Iliuk founded Tymora Analytical last year, which will be located in the Purdue Research Park. The company will begin manufacturing pIMAGO and similar products once it gains investors. 

 

A cancer drug's effectiveness is then exposed by the solution color. A lightly colored solution indicates little kinase activity and shows that the drug was effective. But a darker solution indicates more kinase activity and a less effective drug. 

 

Dr. Wael Harb, an oncologist with Indiana University Health Arnett, said these kinase inhibitors fall into a new generation of cancer drugs that are biologically targeted therapies, many of which he uses to treat some of his cancer patients. 

 

"This kinase (is) a large group of enzymes inside the cells but a lot of them are mutated or overactivated in cancer cells, which might be the culprit causing these cancer cells to grow without control," said Harb, who is also medical director of Horizon Oncology Center. 

 

So designer drugs block kinase activity. However, the difficult part of developing these drugs is screening for effectiveness. "You start with 1,000 drugs in the lab and you are lucky if you get one out of these 1,000 drugs to become part of the clinical trial system," Harb said. "So it's a very costly process and very time consuming." 

 

In his eyes, the pIMAGO nanopolymer research looks promising. 

 

"This is a very hot area of research," he said. "Many companies around the world are developing kinase inhibitors. There is a lot of resources spent on the testing of that. So any progress made in that area can benefit a lot of researchers around the world (who are) working on kinase inhibitors."

 

Tao argues that his nanopolymer would be an easier and less expensive way to test these drugs. Current screening methods include using radioisotopes, which are potentially dangerous due to radiation exposure. Also, antibodies are used to screen kinase inhibitors. 

 

However, since antibodies are in short supply, this can an expensive endeavor, Tao said. 

 

Tao and Iliuk founded Tymora Analytical last year, which will be located in the Purdue Research Park. The company will begin manufacturing pIMAGO and similar products once it gains investors. 

 

Written by
TAYA FLORES
tflores@jconline.com

 

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