Understanding the complex epigenome of advanced renal cell carcinoma may lead to novel epigenomic-based pharmaceutical strategies and identify new targets for therapeutic interventions. Epigenetic changes, such as DNA methylation and histone acetylation, modulate the activity of significant oncogenic signaling pathways by regulating gene expression. Such pathways include the WNT–β-catenin pathway, the von Hippel-Lindau–hypoxia-inducible factor pathway, and epithelial-mesenchymal transition pathway. Common genetic alterations in histone modifier genes in renal cell carcinoma may not only be responsible for the pathogenesis of this disease but also represent potential biomarkers of response to immunotherapies. Rational combinations strategies with histone deacetylase inhibitors are being tested in clinic trials. Renal cell carcinoma represents an ideal setting to dissect the epigenetic-driven changes in the tumor microenvironment that modulate the response to targeted therapies.

了解晚期肾细胞癌的复杂表观基因组可能会导致新的基于表观基因组的药物策略并确定治疗干预的新目标。表观遗传变化，如 DNA 甲基化和组蛋白乙酰化，通过调节基因表达来调节重要致癌信号通路的活性。这些通路包括 WNT-β-catenin 通路、von Hippel-Lindau-缺氧诱导因子通路和上皮间质转化通路。肾细胞癌组蛋白修饰基因的常见遗传改变可能不仅是这种疾病的发病机制，而且还代表了对免疫疗法反应的潜在生物标志物。与组蛋白脱乙酰酶抑制剂的合理组合策略正在临床试验中进行测试。肾细胞癌是剖析肿瘤微环境中表观遗传驱动变化的理想环境，这些变化调节对靶向治疗的反应。