Silver Brian B, Kreutz Anna, Weick Madeleine, Gerrish Kevin, Tokar Erik J
Mechanistic Toxicology Branch, Division of Translational Toxicology (DTT), National Institute of Environmental Health Sciences (NIEHS), Durham, NC, United States.
Molecular Genomics Core, Division of Intramural Research (DIR), National Institute of Environmental Health Sciences (NIEHS), Durham, NC, United States.
Front Oncol. 2024 Apr 19;14:1393930. doi: 10.3389/fonc.2024.1393930. eCollection 2024.
Detrimental side effects of drugs like doxorubicin, which can cause cardiotoxicity, pose barriers for preventing cancer progression, or treating cancer early through molecular interception. Extracellular vesicles (EVs) are valued for their potential as biomarkers of human health, chemical and molecular carcinogenesis, and therapeutics to treat disease at the cellular level. EVs are released both during normal growth and in response to toxicity and cellular death, playing key roles in cellular communication. Consequently, EVs may hold promise as precision biomarkers and therapeutics to prevent or offset damaging off-target effects of chemotherapeutics. EVs have promise as biomarkers of impending cardiotoxicity induced by chemotherapies and as cardioprotective therapeutic agents. However, EVs can also mediate cardiotoxic cues, depending on the identity and past events of their parent cells. Understanding how EVs mediate signaling is critical toward implementing EVs as therapeutic agents to mitigate cardiotoxic effects of chemotherapies. For example, it remains unclear how mixtures of EV populations from cells exposed to toxins or undergoing different stages of cell death contribute to signaling across cardiac tissues. Here, we present our perspective on the outlook of EVs as future clinical tools to mitigate chemotherapy-induced cardiotoxicity, both as biomarkers of impending cardiotoxicity and as cardioprotective agents. Also, we discuss how heterogeneous mixtures of EVs and transient exposures to toxicants may add complexity to predicting outcomes of exogenously applied EVs. Elucidating how EV cargo and signaling properties change during dynamic cellular events may aid precision prevention of cardiotoxicity in anticancer treatments and development of safer chemotherapeutics.
像阿霉素这样的药物会产生有害的副作用，可导致心脏毒性，这对预防癌症进展或通过分子拦截早期治疗癌症构成了障碍。细胞外囊泡（EVs）因其作为人类健康、化学和分子致癌作用的生物标志物以及在细胞水平治疗疾病的疗法的潜力而受到重视。EVs在正常生长过程中以及对毒性和细胞死亡的反应中都会释放，在细胞通讯中发挥关键作用。因此，EVs有望作为精准生物标志物和疗法，以预防或抵消化疗药物的有害脱靶效应。EVs有望成为化疗诱导的心脏毒性的生物标志物以及心脏保护治疗剂。然而，EVs也可以介导心脏毒性信号，这取决于其母细胞的特性和既往事件。了解EVs如何介导信号传导对于将EVs用作减轻化疗心脏毒性的治疗剂至关重要。例如，尚不清楚来自暴露于毒素或处于不同细胞死亡阶段的细胞的EV群体混合物如何在心脏组织中促成信号传导。在此，我们阐述了我们对EVs作为减轻化疗诱导的心脏毒性的未来临床工具的展望，包括作为即将发生的心脏毒性的生物标志物和心脏保护剂。此外，我们还讨论了EVs的异质混合物和短暂接触毒物如何可能增加预测外源性应用EVs结果的复杂性。阐明EV货物和信号特性在动态细胞事件期间如何变化，可能有助于在抗癌治疗中精准预防心脏毒性，并开发更安全的化疗药物。
