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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The importance of TP53 status in cancer therapy: The example of chronic lymphocytic leukemia.
The importance of TP53 status in cancer therapy: The example of chronic lymphocytic leukemia.
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TP53基因编码肿瘤抑制蛋白p53,在维持基因组稳定性和调控细胞周期方面发挥关键作用。约半数人类恶性肿瘤存在TP53突变,该突变与基因组不稳定性增加、化疗耐药及生存率下降等不良临床结局相关。
然而,TP53状态的预后和预测价值在不同癌症类型中并不一致。慢性淋巴细胞白血病(CLL)是TP53改变临床意义明确的一种疾病,该改变会影响治疗决策和患者预后。在CLL中,TP53突变和17p缺失与疾病晚期、对化学免疫治疗耐药及总生存期差密切相关。欧洲CLL研究倡议(ERIC)已将TP53状态确立为关键预后生物标志物,并建议在临床实践中常规检测。鉴于传统疗法治疗TP53突变型CLL存在局限,目前正在探索包括BCL2和BTK抑制剂以及CAR-T 细胞疗法在内的新型靶向治疗,以改善患者结局。本综述深入分析TP53状态在CLL中的演变作用,特别聚焦包括CAR-T 细胞疗法在内的新兴治疗策略及其克服TP53驱动治疗耐药的潜力。
The TP53 gene encodes the tumor suppressor protein p53, which plays a critical role in genomic stability and cell cycle regulation. TP53 mutations are prevalent in approximately half of all human malignancies and are associated with poor clinical outcomes, including increased genomic instability, chemoresistance, and reduced survival rates.
However, the prognostic and predictive value of TP53 status remains inconsistent across cancer types. Chronic lymphocytic leukemia (CLL) stands out as a disease where TP53 alterations have a well-established clinical significance, influencing treatment decisions and patient prognosis. In CLL, TP53 mutations and 17p deletions are strongly correlated with advanced disease stages, resistance to chemo-immunotherapy, and poor overall survival. The European Research Initiative for CLL (ERIC) has recognized TP53 status as a crucial prognostic biomarker, advocating for its routine assessment in clinical practice.
Given the limitations of traditional therapies in TP53 -mutated CLL, novel targeted therapies, including BCL2 and BTK inhibitors, as well as CAR-T cell therapy, are being explored to improve patient outcomes. This review provides an in-depth analysis of the evolving role of TP53 status in CLL, with a particular focus on emerging therapeutic strategies, including CAR-T cell therapy, and their potential to overcome TP53 -driven treatment resistance.
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