a Department of Translational Research and New Technologies in Medicine and Surgery, Laboratory of Medical Genetics , University of Pisa, Medical School , Pisa , Italy.
Expert Rev Gastroenterol Hepatol. 2018 Jan;12(1):49-62. doi: 10.1080/17474124.2017.1374853. Epub 2017 Sep 11.
Our understanding of the epigenetic changes occurring in gastrointestinal cancers has gained tremendous advancements in recent years, and some epigenetic biomarkers are already translated into the clinics for cancer diagnostics. In parallel, pharmacoepigenetics and pharmacoepigenomics of solid tumors are relevant novel, but emerging and promising fields. Areas covered: A comprehensive review of the literature to summarize and update the emerging field of pharmacoepigenetics and pharmacoepigenomics of gastrointestinal cancers. Expert commentary: Several epigenetic modifications have been proposed to account for interindividual variations in drug response in gastrointestinal cancers. Similarly, single-agent or combined strategies with high doses of drugs that target epigenetic modifications (epi-drugs) were scarcely tolerated by the patients, and current research has moved to their combination with standard therapies to achieve chemosensitization, radiosensitization, and immune modulation of cancerous cells. In parallel, recent genome-wide technologies are revealing the pathways that are epigenetically deregulated during cancer-acquired resistance, including those targeted by non-coding RNAs. Indeed, novel, less toxic, and more specific molecules are under investigation to specifically target those pathways. The field is rapidly expanding and gathering together information coming from these investigations has the potential to lead to clinical applications in the coming new years.
近年来,我们对胃肠道癌症中发生的表观遗传变化的理解取得了巨大进展,一些表观遗传生物标志物已经转化为癌症诊断的临床应用。与此同时,实体瘤的药物基因组学和药物遗传学也是相关的新兴但新兴且有前途的领域。
对文献进行全面综述,总结和更新胃肠道癌症药物遗传学和药物遗传学的新兴领域。
已经提出了几种表观遗传修饰来解释胃肠道癌症中药物反应的个体间差异。同样,针对表观遗传修饰的药物(表观遗传学药物)的单药或联合高剂量策略很少被患者耐受,目前的研究已转向将其与标准疗法联合使用,以实现癌症细胞的化疗增敏、放疗增敏和免疫调节。与此同时,最近的全基因组技术揭示了癌症获得性耐药过程中表观遗传失调的途径,包括非编码 RNA 靶向的途径。事实上,正在研究新型、毒性更小、更具特异性的分子,以专门针对这些途径。该领域正在迅速扩展,汇集来自这些研究的信息有可能在未来几年带来临床应用。