Abstract
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.
Highlights
There is a growing burden on the healthcare system with the rise in mortality rate associated with cardiovascular diseases (CVD) and cancer
Indirect effects of cancer drugs on the heart comprising of multiple cell types may trigger a complex integrated response leading to cardiotoxicity (Gintant et al, 2019). induced pluripotent stem cells (iPSCs) technology has enabled mass production of cardiovascular cell types and recapitulate disease phenotypes and pharmacological responses
We summarize the pre-clinical cardio-toxicology studies of chemotherapeutic agents on iPSC-CMs and current limitations associated with the use of iPSC-CMs
Summary
There is a growing burden on the healthcare system with the rise in mortality rate associated with cardiovascular diseases (CVD) and cancer. Chemotherapeutic drugs that inadvertently target the heart causing adverse effects such as ventricular systolic and diastolic dysfunction, arrhythmias, pericarditis, myocardial ischemia and heart failure (Figure 1). These severe cardiovascular risks further contributes to the mortality rate seen in cancer patients (Sarfati et al, 2016; Miller et al, 2019). Due to lack of comprehensive testing and recent expedited approval process for many cancer drugs, there are always concerns regarding efficacy and safety. We summarize the pre-clinical cardio-toxicology studies of chemotherapeutic agents on iPSC-CMs and current limitations associated with the use of iPSC-CMs. we cover the emerging in vitro models that have evolved over the recent decade, offering novel and more predictive alternative for mechanistic assessment of cardiotoxicity and efficacy of oncotherapeutics
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