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A fundamentally new approach to improving cancer chemotherapy

A new strategy for getting anti-cancer drugs to kill cancer cells, without causing serious harm to normal cells in the body, is reported in the current [June] issue of ACS Chemical Biology, a monthly peer-reviewed journal of the American Chemical Society.

The approach, tested in laboratory experiments with several existing anti-cancer drugs, could offer substantial benefits for cancer patients, according to Jeffrey P. Krise, Ph.D. Krise led a group of pharmaceutical and medicinal chemists at the University of Kansas at Lawrence who did the research.

The new approach would allow anticancer drugs to accumulate in both normal and malignant cells. The drugs, however, would be tweaked by giving them "basic" chemical properties. In chemistry, "basic" means an alkaline substance like baking soda or laundry detergent, which has properties opposite those of acidic substances.

Normal cells simply isolate anti-cancer drugs with basic properties, greatly reducing the toxic effects. Cancer cells, in contrast, have an impaired ability to isolate basic substances, and get hit with a full blast of toxicity.

"It could allow cancer patients to tolerate higher and more effective doses of chemotherapy before normal cells are damaged to an extent that causes serious side effects and cessation of therapy," Krise said. "The approach is completely different from previous attempts that were designed to deliver drugs only to cancer cells and not normal cells."

"The results of our studies should lead to the development of rationally designed molecules that are more selective and produce fewer side effects," Krise explained. "Importantly, this technology can also be used to modify existing drugs and increase their selectivity."

Krise’s report describes a number of existing anti-cancer drugs that have basic properties, and notes that the new findings may provide the first explanation of why these drugs are so effective.

"There is obviously much more work to be done in order for the impact of the work to be fully appreciated and accepted," Krise said. "We are hopeful, at the current time, that this technology will have broad applicability."

The research team included Muralikrishna Duvvuri, Ph.D., Samidha Konkar, Ph.D., Kwon Ho Hong, Ph.D., and Brian S. J. Blagg, Ph.D.

Michael Bernstein | EurekAlert!
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