Better Cancer Treatments Ahead? Fewer Chemotherapy Side Effects


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Cisplatin crystals – a chemotherapy drug. Image courtesy of the National Cancer Institute

Has science found a way to reduce chemotherapy side effects?

Researchers from Duke University have isolated the structure of a very important molecule. The transporter molecule, also known as a concentrative nucleoside transporter, can improve the method of carrying chemotherapy drugs into cells. A more efficient method of delivering the drugs to cancer cells means reduced dosages, and fewer side effects for patients.

Interview with Seok-Yong Lee, Ph.D.

The research was published on March 11, in Nature Online. Senior author Seok-Yong Lee, Ph.D., assistant professor of biochemistry at Duke, took the time to elaborate on these advances for Decoded Science.

Decoded Science: What inspired this research?

Dr. Lee: “Having been trained as a biophysicist with expertise in the biological processes of membrane transport, I became interested in a certain class of membrane transporter protein called the solute carrier protein (SLC) family. Solute carrier proteins form a large family of membrane transporters that are designed to carry out nutrient transport across cell membranes.

Humans possess many different solute carrier transporters that vary in the types of nutrients they recognize and their tissue distributions. Interestingly, many drugs actually get into cells by hijacking certain SLC family members. For example, well-known anticancer drugs (Ara-C and gemcitabine) and antiviral drugs (AZT and ribavirin) get inside cells through nucleoside transporters, members of the SLC family. Since the tissue distribution of these transporters is known, knowledge of the mechanism of substrate-specific membrane transport by these transporters will provide a foundation for future drug design to improve bioavailability of the drugs.

We found that there was not a single atomic–level structure available for any member of the nucleoside transporter family, and we knew that solving a structure of one of these transporters would be the key to understanding the inner-workings of nucleoside transporters.”

Decoded Science: What do you consider to be the most important aspect of these results?

Dr. Lee: “By solving the structure of the transporter in complex with a nucleoside, we were able to reveal a molecular picture of how the transporter recognizes its substrate. Understanding this principle can lay the framework for future drug design to improve drug delivery.”

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