Chapter 40 - Outcome of Combining Epigenetic Drugs with Other Treatments in the Clinic

Abstract

Epigenetic modifying drugs are currently being evaluated in numerous clinical trials to treat cancer and other diseases. The US Food and Drug Administration (FDA) has approved 2 DNA methyl transferase (DNMT) inhibitors—azacitidine and decitabine—to treat myelodysplastic syndromes and 3 histone deacetylase (HDAC) inhibitors—vorinostat and romidepsin—to treat cutaneous T-cell lymphoma and belinostat to treat peripheral T-cell lymphoma. Epigenetic modifications lead to reversible global changes that affect diverse cellular processes like proliferation, cell cycle progression, apoptosis, differentiation, and DNA-repair. Apart from their use as single agents in the clinic for specific cancers, preclinical studies show substantial benefits of combining several HDAC inhibitors and DNMT inhibitors with diverse treatment modalities, particularly in solid and hematological malignancies. Though epigenetic modifications are lately associated with several diseases, most of these combinatorial therapies are designed to treat cancer. Limited clinical trials use epigenetic drugs in combination therapies in other diseases. This chapter discusses the potential of combining epigenetic therapies with current treatment modalities. The emphasis lies on either active or completed clinical investigations that have combined epigenetic drugs with existing drugs, exploring better treatment avenues across all diseases.