Schiewer Matthew J, Knudsen Karen E
Sidney Kimmel Cancer Center, Thomas Jefferson University, 233 S 10th St Philadelphia, PA 19107, USA; Department of Cancer Biology, Thomas Jefferson University, 233 S 10th St Philadelphia, PA 19107, USA.
Sidney Kimmel Cancer Center, Thomas Jefferson University, 233 S 10th St Philadelphia, PA 19107, USA; Department of Cancer Biology, Thomas Jefferson University, 233 S 10th St Philadelphia, PA 19107, USA; Department of Urology, Thomas Jefferson University, 233 S 10th St Philadelphia, PA 19107, USA; Department of Radiation Oncology, Thomas Jefferson University, 233 S 10th St Philadelphia, PA 19107, USA.
Trends Endocrinol Metab. 2016 Apr;27(4):216-225. doi: 10.1016/j.tem.2016.02.004. Epub 2016 Mar 1.
DNA damage response and repair (DDR) is a tightly controlled process that serves as a barrier to tumorigenesis. Consequently, DDR is frequently altered in human malignancy, and can be exploited for therapeutic gain either through molecularly targeted therapies or as a consequence of therapeutic agents that induce genotoxic stress. In select tumor types, steroid hormones and cognate receptors serve as major drivers of tumor development/progression, and as such are frequently targets of therapeutic intervention. Recent evidence suggests that the existence of crosstalk mechanisms linking the DDR machinery and hormone signaling pathways cooperate to influence both cancer progression and therapeutic response. These underlying mechanisms and their implications for cancer management will be discussed.
DNA损伤反应与修复(DDR)是一个受到严格调控的过程,它是肿瘤发生的一道屏障。因此,DDR在人类恶性肿瘤中经常发生改变,并且可以通过分子靶向治疗或作为诱导基因毒性应激的治疗药物的结果来用于治疗获益。在某些肿瘤类型中,类固醇激素和同源受体是肿瘤发展/进展的主要驱动因素,因此经常是治疗干预的靶点。最近的证据表明,连接DDR机制和激素信号通路的串扰机制的存在共同影响癌症进展和治疗反应。将讨论这些潜在机制及其对癌症管理的影响。