The Fanconi Anemia/BRCA Signaling Pathway Disruption in Cisplatin-Sensitive Ovarian Cancers
The Fanconi Anemia/BRCA Signaling Pathway Disruption in Cisplatin-Sensitive Ovarian Cancers
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DOI：
10.4161/cc.2.4.413
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发表时间：
2003-01-01
期刊：
影响因子：
4.3
通讯作者：
D'Andrea, Alan D.
中科院分区：
文献类型：
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作者：
D'Andrea, Alan D.
卵巢肿瘤常表现出染色体不稳定性和对化疗药物顺铂的超敏反应。最近，我们已经表明，这种细胞表型可能是由于范可尼贫血/BRCA（FA/BRCA）信号通路的获得性破坏。破坏结果甲基化和沉默的FA基因之一（FANCF），导致顺铂敏感性。该途径的恢复与FANCF的去甲基化相关，导致获得性顺铂耐药。FA/BRCA通路的连续失活和再激活对卵巢癌及相关癌症的诊断和治疗具有重要意义。
Ovarian tumors often exhibit chromosome instability and hypersensitivity to the chemotherapeutic agent cisplatin. Recently, we have shown that this cellular phenotype may result from an acquired disruption of the Fanconi Anemia/BRCA (FA/BRCA) signaling pathway. Disruption results from methylation and silencing of one of the FA genes (FANCF), leading to cisplatin sensitivity. Restoration of this pathway is associated with demethylation of FANCF, leading to acquired cisplatinum resistance. The serial inactivation and reactivation of the FA/BRCA pathway has important implications for the diagnosis and treatment of ovarian cancers and related cancers.