Thomas Dilip, Shenoy Sushma, Sayed Nazish
Stanford Cardiovascular Institute, Stanford, CA, United States.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, United States.
Front Pharmacol. 2021 Feb 18;12:607364. doi: 10.3389/fphar.2021.607364. eCollection 2021.
Cardiovascular disease (CVD) complications have contributed significantly toward poor survival of cancer patients worldwide. These complications that result in myocardial and vascular damage lead to long-term multisystemic disorders. In some patient cohorts, the progression from acute to symptomatic CVD state may be accelerated due to exacerbation of underlying comorbidities such as obesity, diabetes and hypertension. In such situations, cardio-oncologists are often left with a clinical predicament in finding the optimal therapeutic balance to minimize cardiovascular risks and maximize the benefits in treating cancer. Hence, prognostically there is an urgent need for cost-effective, rapid, sensitive and patient-specific screening platform to allow risk-adapted decision making to prevent cancer therapy related cardiotoxicity. In recent years, momentous progress has been made toward the successful derivation of human cardiovascular cells from induced pluripotent stem cells (iPSCs). This technology has not only provided deeper mechanistic insights into basic cardiovascular biology but has also seamlessly integrated within the drug screening and discovery programs for early efficacy and safety evaluation. In this review, we discuss how iPSC-derived cardiovascular cells have been utilized for testing oncotherapeutics to pre-determine patient predisposition to cardiovascular toxicity. Lastly, we highlight the convergence of tissue engineering technologies and precision medicine that can enable patient-specific cardiotoxicity prognosis and treatment on a multi-organ level.
心血管疾病（CVD）并发症是全球癌症患者生存率低下的重要原因。这些导致心肌和血管损伤的并发症会引发长期的多系统疾病。在一些患者群体中，由于肥胖、糖尿病和高血压等潜在合并症的加重，从急性CVD状态发展到有症状的CVD状态的进程可能会加速。在这种情况下，心脏肿瘤学家在寻找最佳治疗平衡以最小化心血管风险并最大化癌症治疗益处时，常常面临临床困境。因此，在预后方面，迫切需要一个具有成本效益、快速、灵敏且针对患者的筛查平台，以便进行风险适应性决策，预防癌症治疗相关的心脏毒性。近年来，从诱导多能干细胞（iPSC）成功衍生出人类心血管细胞方面取得了重大进展。这项技术不仅为基础心血管生物学提供了更深入的机制见解，还无缝整合到药物筛选和发现计划中，用于早期疗效和安全性评估。在这篇综述中，我们讨论了如何利用iPSC衍生的心血管细胞来测试肿瘤治疗药物，以预先确定患者对心血管毒性的易感性。最后，我们强调了组织工程技术和精准医学的融合，这能够在多器官水平上实现针对患者的心脏毒性预后和治疗。
