Correlating Chemical Sensitivity with Low Level Activation of Mechanotransduction Pathways in Hematologic Malignancies.
Correlating Chemical Sensitivity with Low Level Activation of Mechanotransduction Pathways in Hematologic Malignancies.
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DOI：
10.14218/erhm.2017.00022
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发表时间：
2017-07
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影响因子：
--
通讯作者：
Hawley RG
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作者：
Hawley RG
大规模筛选已经揭示，人类造血系统癌细胞系通常比从实体瘤建立的细胞系对各种类型的药物更敏感。对癌症治疗反应门户（http：//portals.broadinstitute.org/ctrp/）中的数据的详细检查表明，这种增强的敏感性是由于造血细胞与非造血细胞相比TAZ-TEAD机械转导途径的激活的基础水平较低。翻译抑制剂，如omacetaxine mepesuccinate（高三尖杉酯碱）属于这类造血选择性化合物。此外，敏感性的其他分子决定因素表明，高三尖杉酯碱可能显示在某些晚期恶性血液病患者的治疗效果，尽管这些途径的激活。
Large-scale screening has revealed that human hematopoietic cancer cell lines are generally more sensitive to various classes of drugs than cell lines established from solid tumors. A detailed examination of data in the Cancer Therapeutics Response Portal (http://portals.broadinstitute.org/ctrp/) suggests that this enhanced sensitivity is due to lower basal levels of activation of TAZ-TEAD mechanotransduction pathways in hematopoietic versus non-hematopoietic cells. Translation inhibitors such as omacetaxine mepesuccinate (homoharringtonine) fall into this category of hematopoietic-selective compounds. Moreover, additional molecular determinants of sensitivity suggest that homoharringtonine might show therapeutic efficacy in certain patients with advanced hematologic malignancies despite activation of these pathways.