超分辨成像方法建立乳腺癌细胞中生长因子受体聚合与蛋白激酶活化之间的定量预测模型

项目名称： 超分辨成像方法建立乳腺癌细胞中生长因子受体聚合与蛋白激酶活化之间的定量预测模型

项目编号： No.31500695

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 张若冰

作者单位： 中国科学院苏州生物医学工程技术研究所

项目金额： 20万元

中文摘要： 抑制特定细胞膜受体——例如人表皮生长因子受体——的靶向生物制剂已被广泛应用于大多数肿瘤类型的研究和临床试验，包括乳腺癌，肺癌，胃肠癌，泌尿系统癌症等等。这些受体通过复杂的信号传递通路激活关键的蛋白激酶，在癌症发生发育中扮演重要角色。然而，在过表达这些受体的病人中，仅有一小部分对特定分子靶向治疗有反应。要改善医疗效果，必须能够识别确定性预测生物标记物并了解它们的生物物理组构，而这依然是非常有挑战性的。这里我们提出用我们的超分辨率成像技术揭示几种关键生长因子受体寡聚的组构状态，结合特别发展的数学工具，建立一个基于图像参数的模型以预测乳腺癌细胞中的蛋白激酶活化，探索癌细胞间非基因因素的异质性。我们的整套技术将极大地促进对乳腺癌发育的了解，并为达到对癌症更知情的个人化分子靶向治疗和更准确的临床预后这一最终目标开辟一个强力有效的方法途径。

中文关键词： 超高分辨；亚细胞结构；定量测定；酶

英文摘要： Targeted biological agents that aim to inhibit specific membrane receptors, such as EGFR and its related family members, have been widely applied in both oncological researches and clinical trials for a majority of tumor types including breast, lung, gastrointestinal and urological malignancies. These receptors are believed to play important roles in cancer development and progression by activating critical protein kinases via complex signaling pathways. However, only a small portion of patients with overexpression of such receptors respond to specific molecular-targeted therapies. Improvement requires identification of definitive predictive biomarkers and biophysical organizations of them, which remain very challenging. Here we propose to use our super-resolution imaging technique to reveal the organizational status of oligomerization of several critical growth factor receptors, and, with developed mathematical tools, to derive an image parameters-based model for the prediction of protein kinase activation in breast cancer cells, probing the non-genetic cell-to-cell heterogeneity. Our suite of technologies will greatly advance the understanding of breast cancer development, and set a potent approach to achieve the ultimate goal of enabling more informed personalized molecular-targeted therapies and more accurate clinical prognosis.

英文关键词： Super-resolution;Subcellular Structures