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. Also, prohibitive cost of immunotherapy can be overcome by therapy that uses relatively inexpensive small molecules. Patients suffer considerable side effects and these may be alleviated by changed drug doses when used in combination with other drugs. Thus investigation of alternative approaches is essential. Recent studies have shed light on the importance of epigenetic regulation in cancer biology including overexpression of histone methyltransferases in cancers and combining inhibitors of epigenetic modifiers may either enhance the efficacy of immunotherapy or treat those patients that have become resistant to therapy.
We hypothesise that:
- combining epigenetic modifier inhibitors with immunotherapy will be more effective compared to using one drug alone.
The aim of this study is to develop a combined therapy using epigenetic modifier inhibitors and immunotherapeutic agents in vivo for the treatment of patients at high risk of recurrence and metastasis.
- Cellular models and treatments.
- Characterisation of the epigenetic modifier change by RNA-seq.
- In vivo mouse model of melanoma.
- Protein complex purification and proteomics.
- Characterisation of putative target genes by ChIP-seq.