First Small Molecule Inhibitors of mRNA-Binding HuR Oncoprotein Identified; Results Hold Promise for Possible Treatments of Wide Variety of Cancers; Molecules May Be Active in Inhibiting Cancer Stem Cells

A team of scientists at the University of Kansas (KU) has pinpointed six chemical compounds that thwart HuR, an "oncoprotein" that binds to RNA and promotes tumor growth. The findings, which could lead to a new class of cancer drugs, were published online on March 9, 2015 in the journal ACS Chemical Biology. The article is titled “Identification and Validation of Novel Small Molecule Disruptors of HuR-mRNA Interaction.” "These are the first reported small-molecule HuR inhibitors that competitively disrupt HuR-RNA binding and release the RNA, thus blocking HuR function as a tumor-promoting protein," said Liang Xu, M.D., Ph.D., Associate Professor of Molecular Biosciences and corresponding author of the paper. The results hold promise for treating a broad array of cancers in people. The researcher said HuR has been detected at high levels in almost every type of cancer tested, including cancers of the colon, prostate, breast, brain, ovaries, pancreas, and lung. "HuR inhibitors may be useful for many types of cancer," Dr. Xu said. "Because HuR is involved in many stem cell pathways, we expect HuR inhibitors will be active in inhibiting 'cancer stem cells,' or the seeds of cancer, which have been a current focus in the cancer drug discovery field." HuR has been studied for many years, but, until now, no direct HuR inhibitors have been discovered, according to Dr. Xu. "The initial compounds reported in this paper can be further optimized and developed as a whole new class of cancer therapy, especially for cancer stem cells," he said. "The success of our study provides a first proof-of-principle that HuR is druggable, which opens a new door for cancer drug discovery. Many other RNA-binding proteins like HuR, which are so far undruggable, can also be tested for drug discovery using our strategy."
Login Or Register To Read Full Story