肿瘤异质性对受体结合的作用-猫眼课题宝

肿瘤异质性对受体结合的作用

批准号：

10132999

负责人：

Margarida Barroso

金额：

$59.9万

依托单位：

RENSSELAER POLYTECHNIC INSTITUTE

依托单位国家：

美国

项目类别：

财政年份：

2017

资助国家：

美国

项目状态：

已结题

起止时间：

2017-04-01 至 2023-03-31

来源：

https://reporter.nih.gov/project-details/10132999

关键词：

3-Dimensional Antibody-drug conjugates Architecture Binding Biological Assay Biological Response Modifier Therapy Biomanufacturing Breast Cancer Cell Cells Characteristics Clinical Collaborations Development Diffusion Drug Carriers Drug Delivery Systems Drug resistance ERBB2 gene Engineering Epidermal Growth Factor Receptor Expression Profiling Fibroblasts Fluorescence Fluorescence Resonance Energy Transfer Goals Heterogeneity Histology Human Image In Vitro Inter-tumoral heterogeneity Interdisciplinary Study Lasers Libraries Ligands Malignant Neoplasms Mammary Neoplasms Measures Membrane Methodology Methods Microscopy Modeling Molecular Target Monitor Nutrient Oncology Optics Patients Personal Satisfaction Pharmaceutical Preparations Prognosis Regimen Resistance Role Spatial Distribution System Systems Development TFRC gene Techniques Technology Therapeutic Therapeutic antibodies Thick Three-Dimensional Imaging Time Variant Writing analytical tool antibody conjugate anticancer treatment base bench to bedside biomarker development bioprinting cancer cell cancer therapy clinically relevant combinatorial cost efficient fluorescence molecular tomography humanized antibody imaging approach imaging platform improved individual patient individualized medicine innovation millimeter molecular imaging neoplastic cell new therapeutic target non-invasive imaging patient response personalized medicine precision medicine programs receptor receptor binding receptor expression scaffold success targeted treatment therapy resistant tool tumor tumor heterogeneity tumorigenesis

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Effect of tumor cell heterogeneity on receptor engagement MPIs: Barroso, Corr and Intes ABSTRACT Precision medicine in oncology has shown great promise in improving patient prognosis and well-being. However, current clinical targeted therapies that act on specific molecular targets associated with cancer have been less effective than anticipated, mainly due to intrinsic and/or relatively rapid acquisition of resistance. Cellular heterogeneity, in particular tumor/stroma compositional heterogeneity and variations in the expression of membrane-bound receptors, has been implicated as an important driver of resistance to anti-cancer treatments. Though, to date, no analytical tool can provide means to replicate these heterogeneities in vitro and can monitor quantitatively the binding of therapeutic antibodies or drug-antibody conjugates to their respective targets, which is critical for drug deliver efficacy. Herein, we propose to integrate a biomanufacturing platform with 3D optical molecular imaging to investigate, for the first time, the influence of tumor cell heterogeneity, namely compositional heterogeneity as well as receptor level expression heterogeneity (i.e., Her2+, EGFR and Tfn), on target-receptor engagement. The unique characteristics of our approach are the ability to manufacture on demand “histology grade” 3D heterogeneous breast tumor systems and quantify ligand-receptor engagement in these systems beyond the current depth limits of microscopy. To achieve our goals, we have assembled a multidisciplinary research team with established expertise and collaboration track record in all facets on the program. Upon completion of this project, we will have integrated this analytical platform to assess receptor engagement of well-known drug carriers in heterogeneous 3D cancer systems. This platform is expected to advance personalized medicine by providing tools and approaches that can be used to critically assess tailored therapy management strategies.

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