CAJ | 학술논문

合成致死(Synthetic lethality)作用即生物体内多个基因共突变时,会造成无法被机体本身调控机制修复的 DNA 损伤,引发细胞凋亡.以 DNA 损伤反应与修复网络为背景,通过细胞信号通路中关键位点基因的共突变,来解决肿瘤细胞治疗过程中的凋亡逃避,为特定基因遗传背景的肿瘤治疗提供了特异性、个体化的治疗方案.三阴性乳腺癌(Triple negative breast cancer,TNBC)通常伴有 brca 基因缺陷,对其合成致死作用的发现和深入研究也为恶性肿瘤治疗提供了新的方向.本文针对目前研究较为透彻的合成致死基因位点的作用原理及意义进行概述,包括 brca、p53、atm/atr 等.同时讨论了合成致死作用在自杀基因系统和药物化疗两种恶性肿瘤治疗方案中可能存在的积极作用.
합성치사(Synthetic lethality)작용즉생물체내다개기인공돌변시,회조성무법피궤체본신조공궤제수복적 DNA 손상,인발세포조망.이 DNA 손상반응여수복망락위배경,통과세포신호통로중관건위점기인적공돌변,래해결종류세포치료과정중적조망도피,위특정기인유전배경적종류치료제공료특이성、개체화적치료방안.삼음성유선암(Triple negative breast cancer,TNBC)통상반유 brca 기인결함,대기합성치사작용적발현화심입연구야위악성종류치료제공료신적방향.본문침대목전연구교위투철적합성치사기인위점적작용원리급의의진행개술,포괄 brca、p53、atm/atr 등.동시토론료합성치사작용재자살기인계통화약물화료량충악성종류치료방안중가능존재적적겁작용.
@@@@ Synthetic lethality is a phenomenon that the cell apoptosis generate when correlative mutations of two or more genes happen in one cell. Regarding the network of DNA damage respond and repair as the background, synthetic lethality may provide a feasible proposal to deal with the apoptosis escapement within cancer cells, and will hopefully give a new method for treating DNA repair-defective human cancers. The defect of brca gene leads this phenomenon in triple negative breast cancer, which is a fundament to further this research. In this review, we discuss recent advances including the breast cancer susceptibility gene, p53, atm/atr and so forth. At the same time, we analyse some appearing pathways in posse when the synthetic lethality phenomenon combined with a system of suicide genes or chemotherapeutics.