Abstract
Therapies targeting epigenetic changes hold promise to prevent drug resistance and improve durability of therapy responses in lung and other cancers. Epigenetic control of gene expression occurs through a variety of dynamic mechanisms, including DNA methylation and histone modifications. Currently, the only epigenetic therapies approved for use in humans are DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors. Clinical trials in lung cancer have shown some promise for combination therapy of DNMT and HDAC inhibitors and for combination of epigenetic inhibitors with targeted therapies. In this review, we describe the rationale for use of epigenetic inhibitors to overcome therapy resistance in cancer, with a focus on the role of epigenetics in resistance to targeted therapies. We also summarize completed and ongoing clinical trials utilizing epigenetic inhibitors in combination with chemotherapy, immunotherapy, and targeted therapies.
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