John Murphy, MDLinx | May 12, 2016
Scientists have for the first time used a rapid computational approach to design a small-molecule drug that targets the specific cancer-causing RNA of one of the hardest to treat cancers—triple-negative breast cancer, according to a study published online May 11, 2016 in the journal Proceedings of the National Academy of Sciences.
In experiments in mice, the compound—Targaprimir-96—triggered apoptosis of only the breast cancer cells, which left other cells unharmed but destroyed breast cancer tumors.
“This is the first example of taking a genetic sequence and designing a drug candidate that works effectively in an animal model against triple-negative breast cancer,” said lead investigator Matthew Disney, PhD, Professor in the Department of Chemistry at the Scripps Research Institute, in Jupiter, FL
“The study represents a clear breakthrough in precision medicine, as this molecule only kills the cancer cells that express the cancer-causing gene—not healthy cells,” Dr. Disney added.
Precision medicine aims to identify drugs that selectively target disease-causing biomolecules. But it’s a slow, laborious process that requires expensive high-throughput screens to test millions of potential drugs just to find a few that affect the biomolecule.
The approach used in this investigation took a shortcut through that process.
For this study, Dr. Disney and colleagues used a computational database they had developed called Informa. This uses a disease-causing biomolecule’s own genetic sequence to quickly identify small-molecule compounds that target and bind to the biomolecule’s folded RNAs, particularly microRNAs.
“These studies may transform the way the lead drugs are identified—by using the genetic makeup of a disease,” Dr. Disney predicted.
In this investigation, the researchers targeted microRNA-96, an oncogenic miRNA that suppresses cancer cell apoptosis. Their result was Targaprimir-96. The researchers then tested the compound in a 21-day course of treatment in mice. Their results showed decreased production of microRNA-96 and increased apoptosis, which significantly reduced tumor growth.
“In the future, we hope to apply this strategy to target other disease-causing RNAs, which range from incurable cancers to important viral pathogens such as Zika and Ebola,” added first author Sai Pradeep Velagapudi, Research Associate in the Disney lab.