Combining epigenetic drugs with immunotherapy in cancer

Suitable for Honours and PhD students

Whereas advances in immune and targeted therapies have made tremendous progress recently, they are effective only in distinct subsets of patients or result in the emergence of drug resistance, and patients suffer considerable side effects. Thus investigation of alternative approaches is essential. Recent studies have shed light on the importance of epigenetic regulation in cancer biology, including overexpression of epigenetic enzymes histone methyltransferases in cancers. Combining inhibitors of epigenetic modifiers with immune checkpoint inhibitors may either enhance the efficacy of immunotherapy or treat those patients that have become resistant to therapy. Side effects from immunotherapy may be alleviated by lower drug doses required when used in combination with other drugs such as small molecule inhibitors. Also, prohibitive cost of immunotherapy can be overcome by therapy that uses relatively inexpensive small molecules.  

HYPOTHESIS

Combining epigenetic inhibitors with immunotherapy will be more effective in treating solid tumours compared to using single drug.

AIM

The aim of this study is to develop a combined therapy using epigenetic small molecule inhibitors and immunotherapeutic agents in vivo for the treatment of patients at high risk of recurrence and metastasis.

APPROACH

1. Cellular models and drug treatments.
2. Gene expression analysis – RNA-seq.
3. In vivo mouse model of cancer.
4. Protein complex purification and proteomics.
5. Characterisation of putative target genes by ChIP-seq.