New Drug Discovery Reduces Chemotherapy Side Effects

​A team of researchers at Duke University in Durham, North Carolina has determined the structure of a key molecule that could help carry chemotherapy and other anti-viral drugs directly into the body’s cells and may promise to help to create more effective drug treatments with fewer side effects for normal, healthy tissue in the future. The results of the Duke team were published in the March 2012 edition of Nature online and study co-author Seok-Yong Lee, Ph.D., assistant professor of biochemistry at Duke, said "Knowing the structure and properties of the transporter molecule may be the key to changing the way that some chemo-therapies, for example, could work in the body to prevent tumor growth."

The newly discovered transporter molecule is called a concentrative nucleotide transporter, and works by moving nucleotides, the building blocks of DNA and RNA, from the outside to the inside of cells. The concentrative nucleotide transporter can also transport nucleotide-like chemotherapy drugs through cell membranes. Once inside the cells, the nucleotide drugs are modified into nucleotides that are incorporated into DNA in a way that blocks malignant tumor cells and prevents them from dividing and functioning further. The researchers say they now believe it is possible to improve the nucleotide drugs so they are instantly recognized by the transporter molecules in certain types of tissue because they discovered the transporter molecule has three forms, and each recognizes different drugs and resides in different tissues. The research represents a breakthrough for chemotherapy patients in that improving the interactions between the transporter and the drug allows physicians to use less of a particular drug to get it inside the tumor cells. Less dosage translates to fewer side effects, and that can be an important consideration in the often difficult chemotherapy process that many cancer patients still undergo every day in this country.

When the shapes of the transporters are known, scientists can design drugs that are better recognized by those transporters. Because healthy cells don't divide as often as tumor cells do, this means decreasing the dosage would still be an effective approach to killing tumors while protecting patients form harmful side effects at the same time. Although Dr. Lee and his team at Duke won a National Institute of General Medical Sciences Award for their work on the new transporters, the group says the next goal will be to try to understand which exact features of the transporters deliver the ability to recognize the chemotherapy drugs and then to design more new drugs that can easily enter the cells and deal effectively with malignant cell growth.