The subject of this month’s newsletter is “Epigenetics” and I’ve included what I think are 3 excellent articles, one which deals with the bones of how you might capitalize on this approach to discover new drugs. The other articles deal more with its application to the treatment to 2 broad categories of disease, that of uncontrolled inflammation and cancer. I hope that you find them all stimulating and provide some food for thought with respect to the approaches that you may be currently using therapeutically to address disease.

The first article, “Drug discovery for epigenetics targets” by Geoffrey A. Holdgate, Catherine Bardelle, Alice Lanne, Jon Read, Daniel H. O'Donovan, James M. Smith, Nidhal Selmi and Robert Sheppard of AstraZeneca give an overview of current epigenetics drug targets and how one might develop approaches for hit identification in these cases. The article also deals with structure-guided chemistry optimization of such hits into candidate molecules. Finally, and importantly, they point out the challenges currently associated with this approach to drug discovery and the potential future of such epigenetic-based approaches to treat disease.

 

The next article deals with the practice of this approach in a specific set of conditions. Ganji Purnachandra Nagaraju, Prameswari Kasa, Begum Dariya, Nagalakshmi Surepalli, Sujatha Peela and Sarfraz Ahmad in their paper, entitled: “Epigenetics and therapeutic targets in gastrointestinal malignancies” discuss how histone deacetylases (HDACs)  and DNA methyltransferases (DMNTs) have a substantial role in the signal and transduction pathways associated with gastrointestinal malignancies. Through these studies they outline those therapeutic targets that are driven by HDACs and DMNTs and the potential clinical benefits that arise from modulating their action.

 

The final article in this month’s offering is from Angelina Osipyan, Deng Chen and Frank J. Dekker of the Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The Netherlands, entitled “Epigenetic regulation in macrophage migration inhibitory factor (MIF)- mediated signaling in cancer and inflammation”. Moving on from the previous article, the authors outline the significance of epigenetics in cancer and inflammation and point out one of the major mediators in both processes, namely macrophage migration inhibitory factor (MIF). It would appear that abnormal expression of this cytokine and its related pathways may be implicated in both cancer and inflammation. The article deals with how epigenetic regulation of the cytokine has the potential to control MIF signaling and hence be of value in treating both cancer and chronic inflammatory disease.  

 

Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD, he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 50 articles in peer-reviewed journals, written several book chapters and has held a number of patents.