Citron Francesca, Fabris Linda
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Cancers (Basel). 2020 Mar 13;12(3):682. doi: 10.3390/cancers12030682.
Extensive efforts recently witnessed the complexity of cancer biology; however, molecular medicine still lacks the ability to elucidate hidden mechanisms for the maintenance of specific subclasses of rare tumors characterized by the silent onset and a poor prognosis (e.g., ovarian cancer, pancreatic cancer, and glioblastoma). Recent mutational fingerprints of human cancers highlighted genomic alteration occurring on epigenetic modulators. In this scenario, the epigenome dependency of cancer orchestrates a broad range of cellular processes critical for tumorigenesis and tumor progression, possibly mediating escaping mechanisms leading to drug resistance. Indeed, in this review, we discuss the pivotal role of chromatin remodeling in shaping the tumor architecture and modulating tumor fitness in a microenvironment-dependent context. We will also present recent advances in the epigenome targeting, posing a particular emphasis on how this knowledge could be translated into a feasible therapeutic approach to individualize clinical settings and improve patient outcomes.
最近大量的研究揭示了癌症生物学的复杂性；然而，分子医学仍然缺乏阐明维持以隐匿性发病和预后不良为特征的特定罕见肿瘤亚类（如卵巢癌、胰腺癌和胶质母细胞瘤）潜在机制的能力。人类癌症最近的突变特征突出了表观遗传调节因子上发生的基因组改变。在这种情况下，癌症的表观基因组依赖性协调了一系列对肿瘤发生和肿瘤进展至关重要的细胞过程，可能介导导致耐药性的逃逸机制。事实上，在本综述中，我们讨论了染色质重塑在塑造肿瘤结构和在微环境依赖的背景下调节肿瘤适应性方面的关键作用。我们还将介绍表观基因组靶向方面的最新进展，特别强调如何将这些知识转化为一种可行的治疗方法，以实现临床治疗的个体化并改善患者预后。
