目前，与受体酪氨酸激酶信号通路相关的路径已成功介导以抑制肿瘤增殖和促进抗血管生成作用用于癌症治疗。酪氨酸激酶抑制剂（TKI）是一类新型化疗药物，已成功应用于有效治疗各种恶性肿瘤。然而，TKI 的潜在毒性和副作用，例如肝毒性和心脏毒性，限制了它们在临床实践中的使用。代谢活化有可能导致毒性影响。许多 TKI 已被证明能够在细胞色素 P450 催化活化后转化为化学活性/潜在毒性代谢物，从而引起严重的不良反应，包括肝毒性，心脏毒性，皮肤毒性，免疫损伤，线粒体损伤和细胞色素 P450 失活。然而，这些化学活性/潜在毒性物种引起毒性的精确机制仍不清楚。此外，我们提出我们的观点，调节反应代谢物的生成可以降低 TKI 的毒性。探索这个问题将提高对代谢活化及其基本机制的理解，促进酪氨酸激酶抑制剂的合理使用。本综述总结了与 TKI 反应代谢物及其相关毒性的最新证据。本文提供了对 TKI 安全使用和多种 TKI 不良反应的预防和治疗的新见解。

At present, receptor tyrosine kinase signaling-related pathways have been successfully mediated to inhibit tumor proliferation and promote anti-angiogenesis effects for cancer therapy. Tyrosine kinase inhibitors (TKIs), a group of novel chemotherapeutic agents, have been applied to treat diverse malignant tumors effectively. However, the latent toxic and side effects of TKIs, such as hepatotoxicity and cardiotoxicity, limit their use in clinical practice. Metabolic activation has the potential to lead to toxic effects. Numerous TKIs have been demonstrated to be transformed into chemically reactive/potentially toxic metabolites following cytochrome P450-catalyzed activation, which causes severe adverse reactions, including hepatotoxicity, cardiotoxicity, skin toxicity, immune injury, mitochondria injury, and cytochrome P450 inactivation. However, the precise mechanisms of how these chemically reactive/potentially toxic species induce toxicity remain poorly understood. In addition, we present our viewpoints that regulating the production of reactive metabolites may decrease the toxicity of TKIs. Exploring this topic will improve understanding of metabolic activation and its underlying mechanisms, promoting the rational use of TKIs. This review summarizes the updated evidence concerning the reactive metabolites of TKIs and the associated toxicities. This paper provides novel insight into the safe use of TKIs and the prevention and treatment of multiple TKIs adverse effects in clinical practice.