Identification of FDA-approved drugs targeting breast cancer stem cells along with biomarkers of sensitivity.
Identification of FDA-approved drugs targeting breast cancer stem cells along with biomarkers of sensitivity.
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DOI：
10.1038/srep02530
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发表时间：
2013
影响因子：
4.6
通讯作者：
Nakshatri, Harikrishna
中科院分区：
文献类型：
--
作者：
Bhat-Nakshatri, Poornima;Goswami, Chirayu P.;Badve, Sunil;Sledge, George W., Jr.;Nakshatri, Harikrishna
最近开发的基于基因组学的工具允许将食品和药物管理局（FDA）批准的药物重新定位为癌症治疗药物，这些药物用于识别靶向乳腺癌干细胞（CSC）的药物。对来自六项研究的CSC的基因表达数据集进行连接图，以鉴定可能改善CSC特有的基因表达模式的药物。全反式维甲酸（ATRA）与CSC基因表达呈负相关。ATRA降低了乳腺癌细胞亚群的乳腺球形成能力，这与诱导凋亡相关，降低了SOX 2的表达，但升高了其拮抗剂CDX 2的表达。SOX 2/CDX 2比值在CSC富集的乳腺癌中具有预后相关性。富含CSC的K-ras突变乳腺癌细胞系对ATRA耐药，MAP激酶抑制剂可逆转该耐药。因此，可以使用SOX 2、CDX 2和K-ras突变/MAPK活化状态作为反应的生物标志物来测试ATRA单独或组合的功效。
Recently developed genomics-based tools are allowing repositioning of Food and Drug Administration (FDA)-approved drugs as cancer treatments, which were employed to identify drugs that target cancer stem cells (CSCs) of breast cancer. Gene expression datasets of CSCs from six studies were subjected to connectivity map to identify drugs that may ameliorate gene expression patterns unique to CSCs. All-trans retinoic acid (ATRA) was negatively connected with gene expression in CSCs. ATRA reduced mammosphere-forming ability of a subset of breast cancer cells, which correlated with induction of apoptosis, reduced expression of SOX2 but elevated expression of its antagonist CDX2. SOX2/CDX2 ratio had prognostic relevance in CSC-enriched breast cancers. K-ras mutant breast cancer cell line enriched for CSCs was resistant to ATRA, which was reversed by MAP kinase inhibitors. Thus, ATRA alone or in combination can be tested for efficacy using SOX2, CDX2, and K-ras mutation/MAPK activation status as biomarkers of response.
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DOI：
10.4161/cc.8.20.9761
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Ginestier C;Wicinski J;Cervera N;Monville F;Finetti P;Bertucci F;Wicha MS;Birnbaum D;Charafe-Jauffret E
通讯作者：
Charafe-Jauffret E
DOI：
10.1073/pnas.0810221106
发表时间：
2009-02-17
影响因子：
11.1
作者：
Klinakis, Apostolos;Szabolcs, Matthias;Efstratiadis, Argiris
通讯作者：
Efstratiadis, Argiris
影响因子：
51.1
作者：
Badve, Sunil;Nakshatri, Harikrishna
通讯作者：
Nakshatri, Harikrishna
影响因子：
3.4
作者：
Bryan, Margarette;Pulte, E. Dianne;Wieder, Robert
通讯作者：
Wieder, Robert
DOI：
10.1097/igc.0b013e318261d89c
发表时间：
2012-09-01
影响因子：
4.8
作者：
Huang, Li-Ping;Yu, Yan-Hong;Wang, Sui-Hai
通讯作者：
Wang, Sui-Hai