Subtype and pathway specific responses to anticancer compounds in breast cancer
Subtype and pathway specific responses to anticancer compounds in breast cancer
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DOI：
10.1073/pnas.1018854108
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发表时间：
2012-02-21
影响因子：
11.1
通讯作者：
Spellman, Paul T.
中科院分区：
文献类型：
--
作者：
Heiser, Laura M.;Sadanandam, Anguraj;Spellman, Paul T.
乳腺癌由分子上不同的亚型组成，这些亚型可能对目前正在开发的靶向通路治疗有不同的反应。乳腺癌细胞系的集合反映了肿瘤中发现的许多分子亚型和途径，表明用候选治疗化合物治疗细胞系可以指导分子亚型、途径和药物反应之间的关联的鉴定。在77种治疗化合物的测试中，几乎所有药物在这些细胞系中显示出差异反应，并且大约三分之一显示出亚型、途径和/或基因组异常特异性反应。这些观察结果提示了反应和耐药性的机制，并可能为开发预测临床反应的分子测定提供信息。
Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.