Utilizing Precision Medicine to elucidate the mechanisms underpinning treatment efficacy

利用精准医学阐明支撑治疗功效的机制

• 批准号: 9905847
• 负责人: Benjamin D. Hopkins
• 金额: $ 24.9万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905847
• 关键词: Acute; Address; Agreement; Biochemical; Biological; Blood Glucose; Cell Cycle Progression; Cell Line; Clinical; Clinical Trials; Collaborations; Data; Data Set; Disease; Drug Combinations; Drug Screening; Feedback; Future; Genetically Engineered Mouse; Genomic approach; Genomics; Glucose; Goals; Hot Spot; Human; Hyperglycemia; In Vitro; Institutes; Insulin; Link; M cell; Malignant Neoplasms; Molecular; Mutation; Organoids; PIK3CA gene; PIK3R3 gene; PLK1 gene; PTEN gene; Pathway interactions; Patient Agents; Patients; Peptide Library; Phosphorylation; Phosphotransferases; Receptor Protein-Tyrosine Kinases; Recurrence; Resistance; Signal Pathway; Site; Substrate Specificity; Therapeutic; Translating; Treatment Efficacy; Validation; Work; Xenograft Model; Xenograft procedure; base; clinical development; drug sensitivity; fly; improved; in vivo; individual response; infancy; inhibitor/antagonist; insight; ketogenic diet; kinase inhibitor; mutant; paralogous gene; patient population; personalized care; precision medicine; precision oncology; prevent; receptor upregulation; response; side effect; src Homology Region 2 Domain; synergism; targeted agent; therapy resistant; treatment response; tumor; tumor growth

Project Summary: Precision oncology is still in its infancy, and while groups envision personalizing care based on the responses of individual tumors there are a wide array of potential uses for the data generated by precision medicine pipelines. Examining data from iterative drug screening performed in collaboration with the Englander Institute of Precision Medicine this project seeks to examine the molecular mechanisms that underpin the efficacy of two PI3K inhibitor based combinations. Specifically aim one explore the impact of the PLK phosphorylation of both wildtype and mutant PI3K to understand the ramifications of this interaction and to identify patient populations who could benefit from combination treatment with PLK and PI3K inhibitors. The second aim seeks to understand the impact of the insulin release that occurs with PI3K inhibitor treatments, and to ask if therapeutic responses can be improved by preventing this feedback. In this manner this project will seek to explain the molecular mechanisms that underlie observations from our precision medicine pipeline and seek to identify patient populations that would benefit from these therapeutic approaches.

项目概要： 精确肿瘤学仍处于起步阶段，虽然团体设想根据患者的反应进行个性化护理， 对于个体肿瘤来说，精准医疗管道产生的数据有着广泛的潜在用途。 检查与英格兰德精密研究所合作进行的迭代药物筛选的数据 该项目旨在研究支持两种PI3K抑制剂疗效的分子机制。 基于组合。具体来说，目的一是探索野生型和非野生型PLK磷酸化的影响。 突变的PI3K，以了解这种相互作用的后果，并确定患者人群， 从PLK和PI3K抑制剂的联合治疗中获益。第二个目的是了解 PI3K抑制剂治疗对胰岛素释放的影响，并询问治疗反应是否可以 通过防止这种反馈来改善。通过这种方式，该项目将寻求解释分子 这些机制是我们精密医学管道观察的基础， 将从这些治疗方法中受益的人群。