An individualized network medicine infrastructure for precision cardio-oncology

用于精准心脏肿瘤学的个性化网络医学基础设施

• 批准号: 9755498
• 负责人: Feixiong Cheng
• 金额: $ 24.9万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755498
• 关键词: Address; Adverse event; Algorithmic Analysis; Algorithms; Animal Model; Animals; Area; Award; Awareness; Big Data; Biological Assay; Biological Markers; Biology; Cancer Etiology; Cancer Patient; Cancer Survivor; Cardiac; Cardiac Myocytes; Cardiotoxicity; Cardiovascular system; Caring; Cells; Combined Modality Therapy; Comorbidity; Complex; Computational algorithm; Coronary Arteriosclerosis; Dana-Farber Cancer Institute; Data; Development; Diagnosis; Discipline; Disease; Drug Interactions; Drug Targeting; Educational Curriculum; Environment; Evaluation; Gene Proteins; Genetic Diseases; Goals; Guidelines; Health Insurance; Heart failure; Heterogeneity; Hospitals; Human; Immune checkpoint inhibitor; Influentials; Infrastructure; Knowledge; Malignant Neoplasms; Medicine; Mentors; Monitor; Myocardial dysfunction; Network-based; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacology; Phase; Play; Polypharmacy; Positioning Attribute; Prevention; Principal Investigator; Productivity; Prognostic Marker; Program Development; Proteasome Inhibitor; Proteins; Reporting; Research; Research Personnel; Research Training; Risk; Role; Science; Surrogate Markers; System; Systems Biology; Techniques; Therapeutic; Therapeutic Agents; Training; United States; Universities; Vocational Guidance; Woman; base; big biomedical data; biomedical informatics; cancer care; cancer cell; cancer therapy; cardioprotection; career; career development; cost; drug development; drug discovery; genetic variant; genome-wide; human interactome; improved outcome; individual patient; innovation; insurance claims; kinase inhibitor; molecular oncology; new therapeutic target; next generation sequencing; novel; novel therapeutics; oncology; patient oriented; pharmacodynamic biomarker; precision medicine; predictive marker; prevent; programs; screening; side effect; tool development; training opportunity; transcriptome; treatment strategy

The growing awareness of cardiac dysfunction by cancer treatment has led to the emerging field of cardio- oncology. However, there are no guidelines in terms of how to prevent and treat the new cardiotoxicity in cancer survivors due to the limited experimental assays. Network medicine – a discipline that seeks to redefine disease and therapeutics from an integrated perspective using systems biology and network science – offers a non-invasive way to identify actionable biomarkers for cardio-oncology. This five-year career development program will develop state-of-the-art systems pharmacology and network medicine approaches in cardio- oncology that focuses on screening, monitoring, and treating cancer survivors with cardiac dysfunction resulting from cancer treatment for facilitating the career goals to the principal investigator (PI), Dr. Feixiong Cheng. With this application, the PI will adhere to a rigorous mentored training curriculum in Northeastern University, Dana-Farber Cancer Institute, and Harvard’s Brigham and Women's Hospital (BWH). The PI’s mentor, Dr. Albert-Laszlo Barabasi, one of the world’s leading experts in the field of network science, has strong collaborative relations with his co-mentors, Drs. Joseph Loscalzo and Sebastian Schneeweiss, in BWH. Dr. Loscalzo, an influential cardiologist, will provide the PI with cardiovascular biology training, career guidance, and scientific advice on the execution of the proposed research plan. Dr. Schneeweiss, a premier pharmacoepidemiologist, will provide the PI with training on applying computationally intensive algorithms for analyzing patient longitudinal big data. This program proposes two specific aims: 1) Development of a state-of- the-art systems pharmacology approach, namely genome-wide positioning systems drug network (GPSDnet) algorithm, to illuminate the landscape of cardiotoxicity to various cancer agents (K99) - The central, unifying hypothesis of GPSDnet is that an integrated, mechanism-based, network approach which incorporates next- generation sequencing data, drug-target networks, drug-induced transcriptome, the human interactome, along with adverse event reports from the FDA’s Adverse Event Reporting System and patient longitudinal data, will prove a novel and effective way for evaluation of cardiotoxicity for current cancer therapies (e.g., multitargeted kinase inhibitors) and new therapies (e.g., immune checkpoint inhibitors); 2) Cardio-oncology perturbation, diagnosis, prevention, and patient care (R00) - The Aim 2 will emphasize the use of network medicine techniques to identify actionable biomarkers (e.g., comorbidity network modules shared by cancer cells and cardiovascular cells/systems) for advancing the characterization of cardio-oncology heterogeneity, thereby achieving the goal of coordinated, patient-centered strategies for treatment and long-term cardiovascular care (e.g., heart failure and coronary artery disease) for cancer survivors. In summary, approval of this K99 award will be invaluable in establishing Dr. Cheng as an independent investigator by exploiting the promise of precision medicine that is in need of experts specializing in network medicine for cardio-oncology.

人们对癌症治疗引起的心脏功能障碍的认识不断提高，导致了心脏领域的新兴领域 然而，目前还没有关于如何预防和治疗新的心脏毒性的指南。 网络医学是一门寻求重新定义的学科。 使用系统生物学和网络科学从综合角度看待疾病和治疗——提供了 以非侵入性方式识别心脏肿瘤学的可行生物标志物。这五年的职业发展。 该计划将开发心脏领域最先进的系统药理学和网络医学方法 专注于筛查、监测和治疗患有心脏功能障碍的癌症幸存者的肿瘤学 为促进首席研究员 (PI) Feixiong 博士实现职业目标而进行的癌症治疗 通过此申请，PI 将遵守东北大学严格的指导培训课程。 大学、达纳法伯癌症研究所和哈佛大学布莱根妇女医院 (BWH)。 导师 Albert-Laszlo Barabasi 博士是网络科学领域世界领先的专家之一。 与他在 BWH 的共同导师 Joseph Loscalzo 博士和 Sebastian Schneeweiss 博士建立了密切的合作关系。 Loscalzo 博士是一位颇具影响力的心脏病专家，将为 PI 提供心血管生物学培训、职业指导、 以及关于执行拟议研究计划的科学建议。 药物流行病学家将为 PI 提供应用计算密集型算法的培训 该计划提出了两个具体目标：1）发展现状。 最先进的系统药理学方法，即全基因组定位系统药物网络（GPSDnet） 算法，阐明各种癌症药物的心脏毒性 (K99) - 中央的、统一的 GPSDnet 的假设是一种集成的、基于机制的网络方法，其中结合了下一步 一代测序数据、药物靶标网络、药物诱导转录组、人类相互作用组等 借助 FDA 不良事件报告系统的不良事件报告和患者纵向数据，将 证明了一种新颖且有效的方法来评估当前癌症疗法的心脏毒性（例如，多靶点 2) 心脏肿瘤学扰动， 诊断、预防和患者护理 (R00) - Aim 2 将强调网络医学的使用 识别可操作的生物标志物的技术（例如，癌细胞共享的共病网络模块和 心血管细胞/系统），以推进心脏肿瘤异质性的表征，从而 实现协调的、以患者为中心的治疗和长期心血管护理策略的目标 （例如，心力衰竭和冠状动脉疾病）癌症幸存者总而言之，批准该 K99 奖项。 通过利用以下承诺，对于将程博士确立为独立研究者将具有无价的价值 精准医疗需要专门从事心血管肿瘤网络医学的专家。