Targeting Integrin Pathways by GLPG-0187 in Medulloblastoma

GLPG-0187 在髓母细胞瘤中靶向整合素通路

基本信息

批准号：
10561603
负责人：
Jeffrey J Olson
金额：
$ 21.95万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-03 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10561603
关键词：
Acceleration Adult Affect Animal Model Cell Adhesion Cell Line Cell Proliferation Cell Survival Cell physiology Cells Chemotherapy and/or radiation Childhood Malignant Brain Tumor Cisplatin Clinic Clinical Cytoplasmic Granules Cytotoxic Chemotherapy Data Development Dose Drug Kinetics Ensure Family Genes Glioma Growth In Vitro Induction of Apoptosis Integrin Signaling Pathway Integrins Intellectual functioning disability Malignant Neoplasms Malignant neoplasm of brain Molecular Neoplasm Metastasis Neurologic Neurons Nude Mice Operative Surgical Procedures Outcome Pathway interactions Patients Pediatric Neoplasm Pharmaceutical Preparations Pilot Projects Research SHH gene Signal Pathway Signal Transduction Solid Subgroup TP53 gene Testing Therapeutic Tissues adhesion receptor antagonist cell growth chemotherapy drug candidate efficacy evaluation in vivo innovation mRNA Expression medulloblastoma mouse model novel novel therapeutic intervention novel therapeutics overexpression phase 1 study physically handicapped pre-clinical precursor cell receptor stem-like cell tumor growth tumor initiation tumor xenograft tumorigenesis

项目摘要

Project Summary Medulloblastoma (MB) is the most malignant pediatric brain tumor. Current treatments for MB patients include surgery, radiotherapy and chemotherapy but unfortunately, many patients remain incurable or suffer significant neurological, intellectual and physical disabilities. Therefore, novel therapeutic approaches are urgently needed. The integrin family of cell adhesion receptors contributes to multiple cellular functions crucial to tumor initiation, progression and metastasis. However, it remains unknown whether targeting integrin signaling has therapeutic benefits in MB. We recently found expression of 1- integrin (ITGB1) is overexpressed in MB tissues. Moreover, GLPG-0187, a broad- spectrum integrin receptor antagonist, significantly inhibits MB cell growth in vitro and in vivo. Based on our novel results, we hypothesize that targeting integrin signaling by GLPG-0187 may lead to novel therapies for MB patients. To test this, we propose to determine the action mechanisms of GLPG-0187’s in MB, and to determine whether GLPG-0187 inhibits tumor growth in MB preclinical animal models. The anticipated results of these studies are functional and mechanistic evaluations for the efficacy of GLPG-0187 in MB, which will accelerate the development of potential therapeutics into clinic for MB.

项目摘要髓母细胞瘤（MB）是最恶性的小儿脑肿瘤。当前治疗 MB患者包括手术，放疗和化学疗法，但不幸的是，许多患者仍然无法治愈或遭受明显的神经，智力和身体状态残疾。因此，迫切需要新颖的治疗方法。整合素细胞粘附受体系列有助于多种细胞功能对肿瘤至关重要启动，进展和转移。但是，尚不清楚是否针对整联蛋白信号传导在MB中具有治疗益处。我们最近发现1-的表达 integrin (ITGB1) is overexpressed in MB tissues.此外，GLPG-0187，一个广泛的光谱整合素受体拮抗剂，显着抑制MB细胞在体外和IN的抑制体内。基于我们的新结果，我们假设通过 GLPG-0187可能会导致MB患者的新疗法。为了测试这一点，我们建议确定MB中GLPG-0187的动作机制，并确定是否是否 GLPG-0187抑制MB临床前动物模型中的肿瘤生长。预期的结果这些研究是GLPG-0187效率的功能和机械评估在MB中，这将加速向MB诊所的潜在治疗发展。