Modeling Precision Cardio-Oncology: Using Human-Induced Pluripotent Stem Cells for Risk Stratification and Prevention.
Modeling Precision Cardio-Oncology: Using Human-Induced Pluripotent Stem Cells for Risk Stratification and Prevention.
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DOI：
10.1007/s11912-021-01066-2
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发表时间：
2021-05-03
影响因子：
4.7
通讯作者：
Brown SA
中科院分区：
文献类型：
--
作者：
Perry TR;Roberts ML;Sunkara B;Maddula R;McLeish T;Gomez J;Lucas J;Rayan D;Patel S;Liang M;Bosnjak ZJ;Brown SA
心血管毒性是癌症幸存者死亡的主要原因，并且由于癌症存活率的提高而变得越来越普遍。在这篇综述中，我们综合了证据，说明如何在源自人诱导多能干细胞 (hiPSC) 的心肌细胞 (CM) 中评估常见癌症治疗药物，如蒽环类药物、人表皮生长因子受体 (HER2) 单克隆抗体和酪氨酸激酶抑制剂 (TKI)，以了解心血管毒性的潜在机制。我们将其置于精准心脏肿瘤学的背景下，这是一个新兴概念，用于个性化预防和管理癌症治疗中的心血管毒性，并考虑到每个患者的独特因素。我们概述了由心脏病学家和肿瘤学家组成的多学科团队与监管机构合作需要解决的步骤，以实现 hiPSC 在精准心脏肿瘤学中的未来应用。目前心血管毒性的预防包括对癌症患者的可改变危险因素进行常规筛查和管理，以及开始使用心脏保护药物。尽管精准心脏肿瘤学最近取得了进展，但知识差距仍然存在，限制了我们准确预测哪些患者会出现心血管毒性的能力。使用患者特异性 CM 进行的研究有助于药理学发现、机械毒性研究和心脏保护途径的识别。 hiPSC 的研究表明，与没有心脏病的患者相比，患有合并症的患者出现更频繁的不良反应。应考虑利用 hiPSC 模型进行进一步的研究，以评估已知心血管危险因素的影响和缓解，包括血压、体重指数 (BMI)、吸烟状况、糖尿病和体力活动在癌症治疗后心血管毒性中的作用。未来的实际应用将取决于对 hiPSC 模型当前使用情况的了解，以便肿瘤学家和心脏病学家共同了解他们改善心脏肿瘤学临床协作实践的潜力。当应用此类体外表征时，假设可以为每个个体分配安全评分，以确定谁更有可能发生心血管毒性。使用 hiPSC 创建个性化模型并最终评估个体治疗的心血管毒性可能有一天会在精准心脏肿瘤学中制定更多针对患者的治疗计划，同时降低心血管疾病 (CVD) 发病率和死亡率。
Cardiovascular toxicity is a leading cause of mortality among cancer survivors and has become increasingly prevalent due to improved cancer survival rates. In this review, we synthesize evidence illustrating how common cancer therapeutic agents, such as anthracyclines, human epidermal growth factors receptors (HER2) monoclonal antibodies, and tyrosine kinase inhibitors (TKIs), have been evaluated in cardiomyocytes (CMs) derived from human-induced pluripotent stem cells (hiPSCs) to understand the underlying mechanisms of cardiovascular toxicity. We place this in the context of precision cardio-oncology, an emerging concept for personalizing the prevention and management of cardiovascular toxicities from cancer therapies, accounting for each individual patient’s unique factors. We outline steps that will need to be addressed by multidisciplinary teams of cardiologists and oncologists in partnership with regulators to implement future applications of hiPSCs in precision cardio-oncology. Current prevention of cardiovascular toxicity involves routine screenings and management of modifiable risk factors for cancer patients, as well as the initiation of cardioprotective medications. Despite recent advancements in precision cardio-oncology, knowledge gaps remain and limit our ability to appropriately predict with precision which patients will develop cardiovascular toxicity. Investigations using patient-specific CMs facilitate pharmacological discovery, mechanistic toxicity studies, and the identification of cardioprotective pathways. Studies with hiPSCs demonstrate that patients with comorbidities have more frequent adverse responses, compared to their counterparts without cardiac disease. Further studies utilizing hiPSC modeling should be considered, to evaluate the impact and mitigation of known cardiovascular risk factors, including blood pressure, body mass index (BMI), smoking status, diabetes, and physical activity in their role in cardiovascular toxicity after cancer therapy. Future real-world applications will depend on understanding the current use of hiPSC modeling in order for oncologists and cardiologists together to inform their potential to improve our clinical collaborative practice in cardio-oncology. When applying such in vitro characterization, it is hypothesized that a safety score can be assigned to each individual to determine who has a greater probability of developing cardiovascular toxicity. Using hiPSCs to create personalized models and ultimately evaluate the cardiovascular toxicity of individuals’ treatments may one day lead to more patient-specific treatment plans in precision cardio-oncology while reducing cardiovascular disease (CVD) morbidity and mortality.
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影响因子：
3.8
作者：
Cohen JD;Babiarz JE;Abrams RM;Guo L;Kameoka S;Chiao E;Taunton J;Kolaja KL
通讯作者：
Kolaja KL
亚型特异性启动子驱动的动作电位成像，用于 hiPSC 衍生心肌细胞中的精确疾病建模和药物测试。
影响因子：
39.3
作者：
Chen Z;Xian W;Bellin M;Dorn T;Tian Q;Goedel A;Dreizehnter L;Schneider CM;Ward-van Oostwaard D;Ng JK;Hinkel R;Pane LS;Mummery CL;Lipp P;Moretti A;Laugwitz KL;Sinnecker D
通讯作者：
Sinnecker D
人类3D心脏微动物的表征和验证，以评估心脏病理变化。
影响因子：
4.6
作者：
Archer CR;Sargeant R;Basak J;Pilling J;Barnes JR;Pointon A
通讯作者：
Pointon A
影响因子：
4.6
作者：
Christidi, Effimia;Huang, Haojun;Brunham, Liam R.
通讯作者：
Brunham, Liam R.
影响因子：
48
作者：
Burridge, Paul W.;Matsa, Elena;Shukla, Praveen;Lin, Ziliang C.;Churko, Jared M.;Ebert, Antje D.;Lan, Feng;Diecke, Sebastian;Huber, Bruno;Mordwinkin, Nicholas M.;Plews, Jordan R.;Abilez, Oscar J.;Cui, Bianxiao;Gold, Joseph D.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.