公开(公告)号：US20140242602A1

公开(公告)日：2014-08-28

申请号：US14131423

申请日：2012-07-06

申请人： Gabriela Chiosis ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes-Dagama ,  Monica L. Guzman ,  Hongliang Zong

发明人： Gabriela Chiosis ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes-Dagama ,  Monica L. Guzman ,  Hongliang Zong

IPC分类号： G01N33/574

CPC分类号： A61K51/0459 ,  A61K31/52 ,  G01N33/5011 ,  G01N33/5017 ,  G01N33/5044 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57426 ,  G01N2500/04 ,  G01N2800/52

摘要： The disclosure provides evidence that the abundance of this particular “oncogenic HSP90” species, which is not dictated by HSP90 expression alone, predicts for sensitivity to HSP90 inhibition therapy, and thus is a biomarker for HSP90 therapy. The disclosure also provides evidence that identifying and measuring the abundance of this oncogenic HSP90 species in tumors predicts of response to HSP90 therapy. “Oncogenic HSP90” is defined herein as the HSP90 fraction that represents a cell stress specific form of chaperone complex, that is expanded and constitutively maintained in the tumor cell context, and that may execute functions necessary to maintain the malignant phenotype. Such roles are not only to regulate the folding of overexpressed (i.e. HER2), mutated (i.e. mB-Raf) or chimeric proteins (i.e. Bcr-Abl), but also to facilitate scaffolding and complex formation of molecules involved in aberrantly activated signaling complexes (i.e. STATS, BCL6).

摘要翻译： 该公开提供了证据表明，单独HSP90表达不规定的特定“致癌HSP90”物种的丰度预测对HSP90抑制疗法的敏感性，因此是HSP90治疗的生物标志物。 本公开还提供了证据，确定和测量肿瘤中这种致癌HSP90物种的丰度预测了对HSP90治疗的反应。 “致癌HSP90”在本文中被定义为代表分子伴侣复合物的细胞应激特异性形式的HSP90级分，其在肿瘤细胞环境中被扩增和组成型维持，并且可以执行维持恶性表型所需的功能。 这样的作用不仅是调节过表达（即HER2），突变（即mB-Raf）或嵌合蛋白（即Bcr-Abl）的折叠，而且还促进涉及异常激活的信号传导复合体的分子的支架和复合物形成 即STATS，BCL6）。

公开(公告)号：US09555137B2

公开(公告)日：2017-01-31

申请号：US14131423

申请日：2012-07-06

申请人： Gabriela Chiosis ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes-Dagama ,  Monica L. Guzman ,  Hongliang Zong

发明人： Gabriela Chiosis ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes-Dagama ,  Monica L. Guzman ,  Hongliang Zong

IPC分类号： G01N33/574 ,  A61K31/52 ,  A61K51/04 ,  G01N33/50

CPC分类号： A61K51/0459 ,  A61K31/52 ,  G01N33/5011 ,  G01N33/5017 ,  G01N33/5044 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57426 ,  G01N2500/04 ,  G01N2800/52

摘要： The disclosure provides evidence that the abundance of this particular “oncogenic HSP90” species, which is not dictated by HSP90 expression alone, predicts for sensitivity to HSP90 inhibition therapy, and thus is a biomarker for HSP90 therapy. The disclosure also provides evidence that identifying and measuring the abundance of this oncogenic HSP90 species in tumors predicts of response to HSP90 therapy. “Oncogenic HSP90” is defined herein as the HSP90 fraction that represents a cell stress specific form of chaperone complex, that is expanded and constitutively maintained in the tumor cell context, and that may execute functions necessary to maintain the malignant phenotype. Such roles are not only to regulate the folding of overexpressed (i.e. HER2), mutated (i.e. mB-Raf) or chimeric proteins (i.e. Bcr-Abl), but also to facilitate scaffolding and complex formation of molecules involved in aberrantly activated signaling complexes (i.e. STATS, BCL6).

摘要翻译： 该公开提供了证据表明，单独HSP90表达不规定的特定“致癌HSP90”物种的丰度预测对HSP90抑制疗法的敏感性，因此是HSP90治疗的生物标志物。 本公开还提供了证据，确定和测量肿瘤中这种致癌HSP90物种的丰度预测了对HSP90治疗的反应。 “致癌HSP90”在本文中被定义为代表分子伴侣复合物的细胞应激特异性形式的HSP90级分，其在肿瘤细胞环境中被扩增和组成型维持，并且可以执行维持恶性表型所需的功能。 这样的作用不仅是调节过表达（即HER2），突变（即mB-Raf）或嵌合蛋白（即Bcr-Abl）的折叠，而且还促进涉及异常激活的信号传导复合体的分子的支架和复合物形成 即STATS，BCL6）。