肿瘤细胞治疗研究
英文原题：TP53-mutated MDS and AML: immune dysregulation, tumor microenvironment, and emerging therapeutic strategies.
TP53突变驱动骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的肿瘤发生和治疗耐药，损害p53调控的功能如凋亡、免疫监视和基因组稳定性，导致免疫逃逸和代谢重编程。
TP53突变可驱动骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的肿瘤发生及治疗耐药，损害细胞凋亡、免疫监视和基因组稳定性等受p53调控的功能，进而导致免疫逃逸和代谢重编程。TP53突变型MDS和AML的肿瘤微环境可通过细胞因子失调、代谢改变和免疫抑制促进白血病进展。目前疗法，包括化疗和去甲基化药物，疗效有限，导致这些高危患者总体生存率较低。然而，新型治疗方法带来希望，包括MDM2抑制剂、p53再激活药物、靶向通路抑制剂（Hedgehog、Wnt、NF-κB）、免疫调节疗法（免疫检查点抑制剂、CAR-T治疗）、代谢干预（脂肪酸代谢、糖酵解）以及基因编辑技术（CRISPR/Cas9、碱基编辑）。本综述探讨TP53突变型MDS和AML中的免疫功能障碍机制，并介绍新兴治疗策略，重点强调整合靶向、代谢和免疫调节疗法，以作为改善患者结局的变革性方法。
TP53 mutations drive oncogenesis and therapeutic resistance in myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML), impairing p53-regulated functions such as apoptosis, immune surveillance, and genomic stability, leading to immune evasion and metabolic reprogramming. The tumor microenvironment in TP53 -mutated MDS and AML fosters leukemic progression through cytokine dysregulation, altered metabolism, and immune suppression. Current therapies, including chemotherapy and hypomethylating agents, offer limited efficacy, resulting in poor overall survival rates for these high-risk patients. However, novel therapeutic approaches provide promising avenues, including MDM2 inhibitors, p53-reactivating agents, pathway-targeted inhibitors (Hedgehog, Wnt, NF- B), immune modulation (checkpoint inhibitors, CAR-T therapy), metabolic interventions (fatty acid metabolism, glycolysis), and gene-editing technologies (CRISPR/Cas9, base editing). This review explores the mechanisms of immune dysfunction in TP53 -mutated MDS and AML while highlighting emerging therapeutic strategies, emphasizing the integration of targeted, metabolic, and immune-modulating therapies as a transformative approach to improve patient outcomes.
MEMBER ACCOUNT
登录成功会直接打开下一页。
