New Technique Selectively Enables Cancer Drugs to Target Malignant Cells while Sparing Healthy Cells

November 2013, Vol 4, No 9 - Value Propositions

Researchers led by Nobuhide Ueki, PhD, Assistant Research Profes­sor, Department of Molecular Genetics & Microbiology, Stony Brook University, have found a new way to get targeted cancer drugs to selectively affect only the cancer cells of a patient and not the healthy cells that are also normally affected by the drug (and cause its toxicity), thereby removing many of the potential side effects of the drugs, which would of course greatly enhance the value of cancer drugs.

Dr Ueki and his Stony Brook team found a way to selectively target cancer cells with prodrugs (ie, precursors of the target drug) that are activated by 2 enzymes, histone deacetylase (HDAC) and a protease called cathepsin L (CTSL). The HDAC and CTSL enzymes have proved to increase their activity in cancer cells, becoming a potential goal for a selective targeted therapy to kill cancer cells.

“We wondered if we could develop drugs to target those 2 enzymes to make a better anticancer drug,” Dr Ueki said. They tested this approach by adding puromycin to HDAC and CTSL, thereby creating a masked cytotoxic agent, which then selectively kills cancer cell lines with the enhanced activity of HDAC and CTSL.

“This cancer-selective cleavage of the masking group is a promising strategy for the next generation of anticancer drug development, and could be applied to many other cytotoxic agents,” Dr Ueki said. He hopes that this technique could help pharmaceutical companies to continue the development of drugs that were previously discontinued because of their severe toxicities. If drug companies “can use this technique, they might be able to use their drug again. The more new drugs are developed, the more chances of successful treatment are increased. That’s our purpose.” The results of this study were recently published (Ueki N, et al. Nat Commun. 2013;4:2735). The study was funded by the National Cancer Institute and the Stony Brook Institute for Clinical and Translational Sciences. Stony Brook University; November 4, 2013