CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Chemotherapy-Induced Cardiotoxicity: Mechanisms, Detection and Emerging Therapies in Cardio-Oncology.
Chemotherapy-Induced Cardiotoxicity: Mechanisms, Detection and Emerging Therapies in Cardio-Oncology.
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癌症仍是全球主要死因之一,预计到2050年年发病人数将超过3500万。现代抗肿瘤治疗提高了生存率,但也伴随越来越多心血管并发症,统称癌症治疗相关心脏功能障碍(CTRCD)。蒽环类药物和HER2靶向治疗是研究最充分的心脏毒性药物。蒽环类药物通过氧化应激、铁稳态紊乱、线粒体功能障碍和抑制拓扑异构酶II等机制,造成不可逆、剂量依赖性心肌损伤,导致进行性心室功能障碍和心力衰竭。曲妥珠单抗等HER2靶向疗法会干扰具有心脏保护作用的ErbB信号,通常引起可逆性心脏损害。其他肿瘤治疗,包括酪氨酸激酶抑制剂、VEGF拮抗剂和免疫检查点抑制剂,可导致高血压、缺血性损伤和免疫介导的心肌炎。
蛋白酶体抑制剂、组蛋白去乙酰化酶抑制剂和CAR-T 细胞疗法等新型治疗进一步扩展了治疗相关心脏毒性的范围。通过多模态策略早期发现CTRCD,有助于及时干预,包括采用整体纵向应变超声心动图评估、心脏磁共振成像,以及连续测量肌钙蛋白和利钠肽。HFA-ICOS评分等风险分层工具可支持个体化监测和治疗规划。预防及管理策略包括使用ACE抑制剂、β受体阻滞剂和dexrazoxane等心脏保护药物,以及正在兴起的SGLT2抑制剂。现代心脏肿瘤学强调多学科、精准化管理,整合早期发现、遗传风险评估和靶向预防,在维持抗肿瘤疗效的同时保护心脏功能,从而改善癌症患者的生存和生活质量。
Cancer remains a leading cause of global mortality, with annual incidence projected to exceed 35 million cases by 2050. Modern antineoplastic therapies have improved survival outcomes at the risk of increasingly associated cardiovascular complications, collectively termed cancer therapy related cardiac dysfunction (CTRCD). Anthracyclines and HER2-targeted therapies remain the most well-characterized cardiotoxic agents. Anthracyclines cause irreversible, dose-dependent myocardial injury through mechanisms including oxidative stress, iron dysregulation, mitochondrial dysfunction, and topoisomerase II inhibition, leading to progressive ventricular dysfunction and heart failure. HER2-directed therapies, such as trastuzumab, interfere with cardioprotective ErbB signaling, typically producing reversible cardiac impairment. Other oncologic treatments - including tyrosine kinase inhibitors, VEGF antagonists, and immune checkpoint inhibitors - contribute to hypertension, ischemic injury, and immune-mediated myocarditis.
Newer modalities, such as proteasome inhibitors, histone deacetylase inhibitors, and CAR T-cell therapy, have expanded the spectrum of treatment-associated cardiotoxicity. Early CTRCD detection through multimodal strategies - including echocardiographic assessment with global longitudinal strain, cardiac magnetic resonance imaging, and serial measurement of troponins and natriuretic peptides - facilitates timely intervention. Risk stratification tools such as the HFA-ICOS score enable personalized monitoring and therapeutic planning.
Preventive and management strategies incorporate cardioprotective agents like ACE inhibitors, -blockers, dexrazoxane, and emerging therapies such as SGLT2 inhibitors. Modern cardio-oncology emphasizes a multidisciplinary, precision-based approach integrating early detection, genetic risk assessment, and targeted prophylaxis to preserve cardiac function while maintaining oncologic efficacy, thereby enhancing both survival and quality of life for cancer patients.
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