PARP inhibitor treatment in ovarian and breast cancer.
PARP inhibitor treatment in ovarian and breast cancer.
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DOI：
10.1016/j.currproblcancer.2010.12.002
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发表时间：
2011-01
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
--
作者：
聚（ADP-核糖）聚合酶（PARP）抑制剂最近引起了人们的兴奋，因为在三阴性乳腺癌（TNBC）中报告了iniparib（BSI 201）[1]和BRCA 1或2相关卵巢癌或乳腺癌与奥拉帕尼（AZ 2281）[2]的活性。这类药物被认为可以增强细胞毒性治疗而不增加副作用，并作为单一药物杀死具有DNA修复缺陷的癌细胞。某些肿瘤细胞基因组的不稳定性使得PARP抑制剂对肿瘤细胞的选择性高于正常细胞。DNA损伤是由复制错误、活性氧的产生以及暴露于紫外线和电离辐射引起的。由这些有害事件引起的这些病变包括点突变、单链断裂（SSB）、双链断裂（DSB）、链内和链间交联。细胞采用多种类型的DNA修复机制：碱基切除修复（BER）、核酸切除修复（NER）、同源重组（HR）、单链退火（SSA）、错配修复（MMR）和非同源末端连接（NHEJ）来定期修复这些损伤。作为DNA修复的结果，受损细胞可以存活，这对正常细胞来说是最佳的，但与肿瘤细胞的目标正好相反，肿瘤细胞在化疗或放疗中发生DNA损伤。此外，修复过程中可能会发生错误，尤其是NHEJ，这可能导致细胞的新异常和功能障碍。某些遗传性疾病，如BRCA 1和BRCA 2突变，以及其他阻止DNA修复的遗传异常与恶性肿瘤风险增加有关。[3]第一章
Poly (ADP-ribose) polymerase (PARP) inhibitors have raised recent excitement because of the activity reported in triple negative breast cancer (TNBC) with iniparib (BSI 201)[1] and BRCA 1 or 2 associated ovarian or breast cancer with olaparib (AZ 2281)[2]. This class of agents is thought to augment cytotoxic therapy without increasing side effects and to kill cancer cells with DNA repair defects as a single agent. The genomic instability of some tumor cells allows PARP inhibitors to have selectivity for the tumor cells over normal cells.DNA damages result from errors in replication, production of reactive oxygen species, and exposure to ultraviolet rays and ionizing radiation. These lesions that result from these noxious events include point mutations, single strand breaks (SSBs), double strand breaks (DSBs), intrastrand and interstrand cross-links. Cells employ multiple types of DNA repair mechanisms: base excision repair (BER), nucleic acid excision repair (NER), homologous recombination (HR), single strand annealing (SSA), Mismatch Repair (MMR), and nonhomologous end joining (NHEJ) to repair these damages on a regular basis. As a result of DNA repair, injured cells can survive, which is optimal for normal cells, but exactly the opposite of the goal for tumor cells that undergo DNA damage in response to chemotherapy or radiation. In addition, errors can occur in the repair process especially with NHEJ that can lead to new abnormalities and dysfunction of the cells. Certain genetic disorders, such as BRCA1 and BRCA2 mutations, as well as other genetic anomalies that prevent DNA repair are associated with increased risk of malignancies.[3]
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影响因子：
4.3
作者：
D'Andrea, Alan D.
通讯作者：
D'Andrea, Alan D.
影响因子：
6.2
作者：
Cass, I;Baldwin, RL;Karlan, BY
通讯作者：
Karlan, BY
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
4.7
作者：
BURKLE, A;CHEN, G;ZELLER, WJ
通讯作者：
ZELLER, WJ
DOI：
10.1016/0005-2787(71)90012-8
发表时间：
1971-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CLARK, JB;FERRIS, GM;PINDER, S
通讯作者：
PINDER, S