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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

基本信息

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
项目类别：
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

项目摘要

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.

随着人们对癌症治疗引起的心功能障碍的认识不断提高，心脏科也应运而生