Small molecule inhibition of RNA binding proteins in haematologic cancer.

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Public Summary:
Gene expression is a finely tuned, intricate process that normally regulates cellular identity, and becomes disrupted in cancer. One class of molecules inside cells that contribute to gene expression are the so-called RNA binding proteins, defined as proteins whose function is to bind ribonucleic acids (RNA). These proteins participate in gene expression by regulating messenger RNA (mRNAs), which in turn are made into proteins. Some of these RNA binding proteins are known to play roles in cancers, and specifically in blood cancers. In this article, we examine the work of other scientists who have developed various ways to counteract the functions of these RNA binding proteins using chemicals, which have the potential to be turned into cancer drugs. Recent advances have made it possible to generate these molecules in more efficient and better ways, as well as to make these chemicals more effective against cancer cells. This publication serves to establish what is known, to inform our own efforts, funded by CIRM, to generate novel methods to target cancer stem cells.
Scientific Abstract:
In recent years, advances in biomedicine have revealed an important role for post-transcriptional mechanisms of gene expression regulation in pathologic conditions. In cancer in general and leukaemia specifically, RNA binding proteins have emerged as important regulator of RNA homoeostasis that are often dysregulated in the disease state. Having established the importance of these pathogenetic mechanisms, there have been a number of efforts to target RNA binding proteins using oligonucleotide-based strategies, as well as with small organic molecules. The field is at an exciting inflection point with the convergence of biomedical knowledge, small molecule screening strategies and improved chemical methods for synthesis and construction of sophisticated small molecules. Here, we review the mechanisms of post-transcriptional gene regulation, specifically in leukaemia, current small-molecule based efforts to target RNA binding proteins, and future prospects.