Heart Failure in Cancer Patients

癌症患者的心力衰竭

• 批准号: 9284514
• 负责人: Hind Lal
• 金额: $ 39.5万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9284514
• 关键词: Address; Adverse effects; Affect; Animal Model; Antineoplastic Agents; Area; Awareness; BAY 54-9085; Cachexia; Cancer Model; Cancer Patient; Cardiac; Cardiotoxicity; Cardiovascular system; Cause of Death; Cessation of life; Clinic; Clinical; Clinical Trials; Comorbidity; Data; Development; Diagnosis; Drug Targeting; Drug usage; FDA approved; Face; Fishes; Functional disorder; Future; Hand; Health Care Costs; Heart; Heart failure; Impairment; Incidence; Knowledge; Lead; Malignant Neoplasms; Mediating; Modeling; Molecular; Morbidity - disease rate; Mus; Myocardial dysfunction; Oligonucleotides; Oncologist; Pathology; Patients; Pharmaceutical Preparations; Phosphotransferases; Physicians; Play; Process; Protein Kinase; Protein Kinase Inhibitors; Publishing; Quality of life; Reproducibility; Rodent Model; Role; Scourge; Sentinel; Signal Pathway; Stress; Testing; Therapeutic; Toxic effect; Transgenic Organisms; Work; Zebrafish; base; cancer cachexia; cancer therapy; cardiac cachexia; injured; kinase inhibitor; knock-down; mortality; mouse model; novel diagnostics; novel strategies; novel therapeutic intervention; pre-clinical; prevent; prophylactic; protein kinase inhibitor; public health relevance; screening; small molecule; targeted treatment; tool; virtual; wasting; Address; Adverse effects; Affect; Animal Model; Antineoplastic Agents; Area; Awareness; BAY 54-9085; Cachexia; Cancer Model; Cancer Patient; Cardiac; Cardiotoxicity; Cardiovascular system; Cause of Death; Cessation of life; Clinic; Clinical; Clinical Trials; Comorbidity; Data; Development; Diagnosis; Drug Targeting; Drug usage; FDA approved; Face; Fishes; Functional disorder; Future; Hand; Health Care Costs; Heart; Heart failure; Impairment; Incidence; Knowledge; Lead; Malignant Neoplasms; Mediating; Modeling; Molecular; Morbidity - disease rate; Mus; Myocardial dysfunction; Oligonucleotides; Oncologist; Pathology; Patients; Pharmaceutical Preparations; Phosphotransferases; Physicians; Play; Process; Protein Kinase; Protein Kinase Inhibitors; Publishing; Quality of life; Reproducibility; Rodent Model; Role; Scourge; Sentinel; Signal Pathway; Stress; Testing; Therapeutic; Toxic effect; Transgenic Organisms; Work; Zebrafish; base; cancer cachexia; cancer therapy; cardiac cachexia; injured; kinase inhibitor; knock-down; mortality; mouse model; novel diagnostics; novel strategies; novel therapeutic intervention; pre-clinical; prevent; prophylactic; protein kinase inhibitor; public health relevance; screening; small molecule; targeted treatment; tool; virtual; wasting

DESCRIPTION (provided by applicant): This Project is focused on two critical issues that many cancer patients have to face: 1) the cardiotoxicity resulting from the use of anti-cancer drugs that injure the heart and 2) the cardiac dysfunction that arises from cancer induced cardiac cachexia. Neither of these issues are sufficiently appreciated by physicians, and this leads to morbidity and, in some cases, mortality. In this Project we propose to address these deficiencies. In Aim 1 we propose to employ the zebrafish as a tool to identify anti-cancer drugs from the class of protein kinase inhibitors. Whereas rodent models have not been very effective in identifying problematic kinase inhibitors, our preliminary studies suggest the zebrafish may be a viable sentinel. We have, and will, test this hypothesis on each of the 12 drugs that are currently on the market, and on additional agents that will reach the market in the future. Furthermore, we will use these drugs as tools to identify the roles played by various protein kinases in the heart- an area about which we know very little. This should allow us to predict problematic agents before they are in widespread use. The second issue will address is cancer-induced cardiac cachexia, its consequences on the heart, and the signaling pathways that regulate it. Cachexia and its sequellae are estimated to be the cause of death in approximately 30% of cancer patients. Most importantly, we have outlined strategies, based on our findings in rodent models that limit or prevent cancer-induced cardiac cachexia. Remarkably, these strategies rely on agents that have been used in heart failure patients for years. Since these drugs are already FDA-approved for use in heart failure patients, we are proposing to go to clinical trial with these agents if our findings in additional rodent models concur with our completed studies. In summary, we believe that our studies could lead to novel diagnostic and therapeutic approaches to better the lives of cancer victims.

描述（由申请人提供）：该项目集中在许多癌症患者必须面对的两个关键问题上：1）使用抗癌药物造成心脏伤害的抗癌药物和2）癌症引起的心脏功能障碍引起的心脏功能障碍引起的心脏功能障碍引起的心脏功能障碍。这些问题都没有得到医生的充分理解，这导致了发病率，在某些情况下是死亡率。在这个项目中，我们建议解决这些缺陷。在AIM 1中，我们建议使用斑马鱼作为一种工具来鉴定蛋白激酶抑制剂类别的抗癌药物。尽管啮齿动物模型在鉴定有问题的激酶抑制剂方面并不是很有效，但我们的初步研究表明斑马鱼可能是可行的前哨。我们已经并且将对当前市场上的12种药物以及将来将来进入市场的其他代理商中的每种假设进行测试。此外，我们将使用这些药物作为工具来确定各种蛋白激酶在心脏中所扮演的角色，而我们对此一无所知。这应该使我们能够在广泛使用之前预测有问题的代理。第二个问题将解决癌症引起的心脏恶病质，其对心脏的后果以及调节它的信号通路。据估计，在大约30％的癌症患者中，恶病质及其后遗症是死亡原因。最重要的是，我们根据数限制或预防癌症引起的心脏恶病质的发现的发现，概述了策略。值得注意的是，这些策略依赖于多年来在心力衰竭患者中使用的药物。由于这些药物已经被FDA批准用于心力衰竭患者，因此，如果我们在其他啮齿动物模型中的发现与我们的完整研究同意，我们建议与这些药物一起进行临床试验。总而言之，我们认为我们的研究可能会导致新颖的诊断和治疗方法，以改善癌症受害者的生活。