Epigenetic targeting and histone deacetylase inhibition in RCC

Epigenetic regulation through histone modifications and DNA methylation of critical genes involved in cell cycle regulation, invasion, metastasis, and tumor-induced angiogenesis has been shown to play an important role in cancer development. Epigenetic changes are potentially reversible and therefore represent a target for therapeutic intervention with the potential of modulating oncogenes/tumor suppressor genes involved in the initiation and progression of cancer. Rational combination strategies that take advantage of transcriptional and posttranslational modifications induced by histone deacetylase inhibitors have generated promising preclinical results and are actively being tested in clinical trials. Preclinical and clinical evidence suggests that kidney tumors are ideal candidates for epigenetic therapies in view of specific mutations in histone modifier genes, overexpression of angiogenesis factors, and intrinsic sensitivity to immunotherapies. This chapter focuses on epigenetic changes in renal cell carcinoma (RCC) and, in particular, on histone modifications and therapeutic approaches currently underway targeting these epigenetic changes.