Pharmacogenomics of platinum-based chemotherapy in NSCLC.

Pharmacogenomics of platinum-based chemotherapy in NSCLC.
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NSCLC中基于铂的化学疗法的药物基因组学。

DOI:
10.1517/17425250902973711
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发表时间:
2009-07
影响因子:
4.3
通讯作者:
Wu X
Wu X
中科院分区:
医学2区
文献类型:
--
作者:
Hildebrandt MA;Gu J;Wu X

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NSCLC是美国癌症相关死亡的主要原因。NSCLC患者大多接受含铂化疗,通常与放射治疗联合使用。然而,化学抗性的发展是限制治疗成功的主要障碍。在这篇综述中,我们总结了目前的理解的遗传因素调节化疗耐药性铂类化疗药物及其与临床结果的非小细胞肺癌患者。我们专注于负责药物流入和流出,代谢和解毒,DNA损伤修复以及其他调节铂类药物治疗效果的下游细胞过程的候选途径。我们还讨论了基于通路的多基因和全基因组方法在确定NSCLC临床结局中涉及的遗传因素中的应用。总体而言,目前的研究表明,每个个体多态性对临床结局的影响是适度的,这表明需要一种更全面的方法,包括多基因,表型,流行病学和临床变量,以预测接受铂类化疗的NSCLC患者的预后。
NSCLC is the leading cause of cancer-related death in the US. Patients with NSCLC are mostly treated with platinum-based chemotherapy, often in combination with radiation therapy. However, the development of chemoresistance is a major hurdle limiting treatment success. In this review, we summarize the current understanding of the genetic factors modulating chemoresistance to platinum chemotherapeutics and their association with clinical outcomes for NSCLC patients. We focus on candidate pathways responsible for drug influx and efflux, metabolism and detoxification, DNA damage repair, and other downstream cellular processes that modulate the effect of platinum-based therapy. We also discuss the application of pathway-based polygenic and genome-wide approaches in identifying genetic factors involved in NSCLC clinical outcomes. Overall, current studies have shown that the effects of each individual polymorphism on clinical outcomes are modest suggesting that a more comprehensive approach that incorporates polygenetic, phenotypic, epidemiologic and clinical variables will be necessary to predict prognosis for NSCLC patients receiving platinum-based chemotherapeutics.
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