5-Fluorouracil response in a large panel of colorectal cancer cell lines is associated with mismatch repair deficiency.
5-Fluorouracil response in a large panel of colorectal cancer cell lines is associated with mismatch repair deficiency.
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DOI：
10.1038/sj.bjc.6605780
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发表时间：
2010-07-27
影响因子：
8.8
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中科院分区：
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结直肠癌（CRC）是最常见的癌症之一，其治疗仍然基于很少的药物。目前，没有生物学标准用于选择最有效的既定药物进行治疗。采用SRB法检测77个结直肠癌细胞系对5-氟尿嘧啶（5FU）的敏感性。这些反应被分为三类，并与细胞系的遗传变化相关。5-氟尿嘧啶反应与复制错误状态（错配修复缺陷）之间的相关性最强且最明确。所有其他重要的相关性（DCC杂合性缺失和TGFbIIR突变）都是与复制错误状态相关的次要因素。我们的研究结果验证了先前主要基于临床数据的分析，并表明复制错误状态可能是基于5-氟尿嘧啶的CRC治疗的有用指南。从本质上讲，所有先前描述的与5FU响应的相关性都是次要的，而不是与复制错误状态的关联。
Colorectal cancer is (CRC) one of the commonest cancers and its therapy is still based on few drugs. Currently, no biological criteria are used to choose the most effective of the established drugs for treatment. A panel of 77 CRC cell lines was tested for sensitivity to 5-fluorouracil (5FU) using the SRB assay. The responses were grouped into three categories and correlated with genetic changes in the cell lines. The strongest and most clearcut correlation was between 5-fluorouracil response and replication error status (mismatch repair deficiency). All the other significant correlations (loss of heterozygosity for DCC and mutations in TGFbIIR) are secondary to the association with replication error status. Our findings validate previous analyses based mainly on clinical data, and indicate that replication error status could be a useful guide to 5-fluorouracil-based CRC therapy. Essentially, all previously described correlations with 5FU response are secondary to the association with replication error status.