Curigliano Giuseppe
Early Drug Development for Innovative Therapy Division, European Institute of Oncology, Via Ripamonti, 435 20141, Milan, Italy.
Handb Exp Pharmacol. 2018;249:161-180. doi: 10.1007/164_2017_31.
Genomic instability is a characteristic of most human cancers and plays critical roles in both cancer development and progression. There are various forms of genomic instability arising from many different pathways, such as DNA damage from endogenous and exogenous sources, centrosome amplification, telomere damage, and epigenetic modifications. DNA-repair pathways can enable tumor cells to survive DNA damage. The failure to respond to DNA damage is a characteristic associated with genomic instability. Understanding of genomic instability in cancer is still very limited, but the further understanding of the molecular mechanisms through which the DNA damage response (DDR) operates, in combination with the elucidation of the genetic interactions between DDR pathways and other cell pathways, will provide therapeutic opportunities for the personalized medicine of cancer.
基因组不稳定是大多数人类癌症的一个特征,在癌症的发生和发展中都起着关键作用。基因组不稳定有多种形式,源于许多不同的途径,如内源性和外源性来源的DNA损伤、中心体扩增、端粒损伤和表观遗传修饰。DNA修复途径能使肿瘤细胞在DNA损伤中存活。对DNA损伤无反应是与基因组不稳定相关的一个特征。目前对癌症中基因组不稳定的了解仍然非常有限,但进一步了解DNA损伤反应(DDR)的分子机制,以及阐明DDR途径与其他细胞途径之间的遗传相互作用,将为癌症的个性化医疗提供治疗机会。