Perše Martina
Medical Experimental Centre, Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Biomedicines. 2021 Oct 7;9(10):1406. doi: 10.3390/biomedicines9101406.
Cisplatin is one of the most widely used chemotherapeutic drugs in the treatment of a wide range of pediatric and adult malignances. However, it has various side effects which limit its use. Cisplatin mouse models are widely used in studies investigating cisplatin therapeutic and toxic effects. However, despite numerous promising results, no significant improvement in treatment outcome has been achieved in humans. There are many drawbacks in the currently used cisplatin protocols in mice. In the paper, the most characterized cisplatin protocols are summarized together with weaknesses that need to be improved in future studies, including hydration and supportive care. As demonstrated, mice respond to cisplatin treatment in similar ways to humans. The paper thus aims to illustrate the complexity of cisplatin side effects (nephrotoxicity, gastrointestinal toxicity, neurotoxicity, ototoxicity and myelotoxicity) and the interconnectedness and interdependence of pathomechanisms among tissues and organs in a dose- and time-dependent manner. The paper offers knowledge that can help design future studies more efficiently and interpret study outcomes more critically. If we want to understand molecular mechanisms and find therapeutic agents that would have a potential benefit in clinics, we need to change our approach and start to treat animals as patients and not as tools.
顺铂是治疗多种儿科和成人恶性肿瘤最广泛使用的化疗药物之一。然而，它有各种副作用，限制了其使用。顺铂小鼠模型广泛用于研究顺铂的治疗和毒性作用。然而，尽管有许多有前景的结果，但在人类治疗结果方面尚未取得显著改善。目前在小鼠中使用的顺铂方案存在许多缺点。本文总结了最具代表性的顺铂方案以及未来研究中需要改进的弱点，包括水化和支持治疗。如前所示，小鼠对顺铂治疗的反应与人类相似。因此，本文旨在说明顺铂副作用（肾毒性、胃肠道毒性、神经毒性、耳毒性和骨髓毒性）的复杂性，以及组织和器官之间病理机制在剂量和时间依赖性方式下的相互联系和相互依存关系。本文提供的知识有助于更有效地设计未来研究，并更严格地解释研究结果。如果我们想了解分子机制并找到可能在临床上有潜在益处的治疗药物，我们需要改变方法，开始将动物视为患者而非工具。
