Targeting epigenome by drug repositioning and by natural products

Drug repositioning refers to finding new targets of old drugs, for example anti-malarial drugs can be used to block autophagy in cancer stem cells.

Our interest is to screen for the inhibitors of epigenetic modifiers that result in aberrant expression in cancer stem cells, from a library of ‘old’ drugs. Epigenetic control of transcription is the central mechanism controlling cell fate choice and is reported to be the key player in many cancers. We are interested to find drugs that can inhibit histone deacetylase (HDAC), histone demethylase family (JMJD2) family of proteins.

HDAC inhibitors are useful chemotherapeutic agents for the treatment of Lymphoma; however, isotype selective HDAC inhibitors are needed for selective treatment of cancer cells without affecting non-malignant cells.

Similarly, Jumonji family of histone demethylases is known to be over expressed in various cancers and in collaboration with other proto-oncogenes it maintains the malignant gene expression programme. Inhibiting JMJD2 can be beneficial in various different cancers. The first screen of inhibitors will be based on in silico motif screening and potential drugs will be tested in cell culture assays.

Using cell culture based assays we plan to test the potential targets by testing the proliferation and changes in the gene expression profiles and microarrays. In addition, in vitro enzyme assays will be performed to confirm the target. Target characterization and validation will also be performed on primary patient samples. Finding new targets for old drug can rejuvenate some neglected compounds and it will circumvent the issue of clinical trials and licencing.

Any enquiries relating to the project and/or suitability should be directed to Dr Athar Aziz, [Email Address Removed]

For more information on research within the School of Environment and Life Sciences please visit the School research website www.salford.ac.uk/environment-life-sciences/research