Epigenetic therapy and chemosensitization in solid malignancy

Epigenetic modifications result in dynamic shifts between transcriptionally active and suppressed states. The potentially reversible nature of epigenetic changes underlies the concept of epigenetic therapy, which serves to reprogram cancer cells as opposed to inducing cytotoxicity that occurs with standard chemotherapeutics. There are numerous enzymes involved in epigenetic changes and each can be potentially targetable. Although many investigations have evaluated the clinical potential of the various epigenetic therapies, currently only histone deacetylase inhibitors and DNA methyltransferase inhibitors are approved for use in specific hematologic malignancies. Use of epigenetic therapy coincident with cytotoxic or targeted systemic therapy appears to derive a benefit due to chemosensitization. Trials demonstrating efficacy from combination therapy have been performed in various diseases such as NSCLC, ovarian cancer and breast cancer. Furthermore, there are patient subsets in certain solid tumors in which epigenetic therapy provide durable response, such as patients with NSCLC and specific hypermethylation patterns. The encouraging results from combination therapy identified in these trials built upon prior investigations and have provided a foundation for ensuing trials seeking to evaluate epigenetic therapy.