决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Cardiotoxicity of Antitumor Agents: Therapeutic Challenges in Heart Failure with Reduced and Preserved Ejection Fraction.
Cardiotoxicity of Antitumor Agents: Therapeutic Challenges in Heart Failure with Reduced and Preserved Ejection Fraction.
肿瘤治疗的显著进展极大地提高了癌症生存率,但同时也带来了沉重的心血管并发症负担。
肿瘤治疗的显著进展极大地提高了癌症生存率,但同时引入了沉重的心血管并发症负担。心脏肿瘤学已崛起为一个关键的多学科领域,致力于减轻从传统化疗药物到新型免疫治疗等救命抗癌治疗带来的“附带损伤”。本综述全面分析了癌症治疗相关心功能障碍(CTRCD)的病理生理机制、临床表型和不断演变的管理策略。对当前文献进行了广泛综合,重点关注心脏毒性的分子通路,包括蒽环类药物对拓扑异构酶II的抑制、靶向药物对HER2信号通路的干扰,以及检查点抑制剂(ICIs)触发的免疫介导性心肌炎。心脏毒性日益被视为一组表型谱系。射血分数降低的心力衰竭(HFrEF)仍是细胞毒性药物的主要关注点,而射血分数保留的心力衰竭(HFpEF)正逐渐成为放射治疗和酪氨酸激酶抑制剂(TKIs)的重要并发症。先进诊断工具的整合——特别是整体纵向应变(GLS)和心脏磁共振(CMR)映射——已将临床焦点转向亚临床检测。此外,PRADA和SUCCOUR等关键临床试验已验证了早期药物预防和应变指导下的干预措施。本文还探讨了新出现的挑战,包括CAR-T细胞诱导的细胞因子释放综合征的管理以及儿科和老年人群特定的心血管需求。心脏肿瘤学的未来在于精准医学,利用基因组分析和人工智能识别高风险个体。积极主动的多学科方法对于确保现代肿瘤学的成功不因不可逆的心血管疾病而受损至关重要。
The remarkable evolution of oncological therapies has dramatically improved cancer survival rates but has simultaneously introduced a significant burden of cardiovascular complications. Cardio-oncology has emerged as a critical multidisciplinary field focused on mitigating the "collateral damage" of life-saving anticancer treatments, ranging from traditional chemotherapeutics to novel immunotherapies. This review provides a comprehensive analysis of the pathophysiological mechanisms, clinical phenotypes, and evolving management strategies for cancer therapy-related cardiac dysfunction (CTRCD). An extensive synthesis of the current literature was conducted, focusing on the molecular pathways of cardiotoxicity, including Topoisomerase II inhibition by anthracyclines, HER2 signaling disruption by targeted agents, and immune-mediated myocarditis triggered by checkpoint inhibitors (ICIs). Cardiotoxicity is increasingly recognized as a spectrum of phenotypes. Heart failure with reduced ejection fraction (HFrEF) remains a primary concern with cytotoxic agents, while heart failure with preserved ejection fraction (HFpEF) is emerging as a critical complication of radiation therapy and tyrosine kinase inhibitors (TKIs). The integration of advanced diagnostic tools-specifically Global Longitudinal Strain (GLS) and Cardiac Magnetic Resonance (CMR) mapping-has shifted the clinical focus toward subclinical detection. Furthermore, pivotal clinical trials such as PRADA and SUCCOUR have validated early pharmacological prophylaxis and strain-guided interventions. Emerging challenges, including the management of CAR-T cell-induced cytokine release syndrome and the specific cardiovascular needs of pediatric and geriatric populations, are also explored. The future of cardio-oncology lies in precision medicine, leveraging genomic profiling and artificial intelligence to identify high-risk individuals. A proactive, multidisciplinary approach is essential to ensure that the success of modern oncology is not compromised by irreversible cardiovascular morbidity.
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