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:B-cell lymphoma: Advances in pathogenesis, diagnosis, and targeted therapies.
B-cell lymphoma: Advances in pathogenesis, diagnosis, and targeted therapies.
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B细胞淋巴瘤(BCL)是一组异质性血液系统恶性肿瘤,起源于B淋巴细胞,具有多样的临床表现和分子特征。本综述重点介绍对其发病机制的认识、诊断方法进展及治疗策略发展。染色体易位(如t(14;18)、MYC重排)、TP53等肿瘤抑制基因突变,以及B细胞受体(BCR)、NF-κB、PI3K/AKT和JAK/STAT等关键信号通路异常,均是疾病发生的核心因素。
此外,非编码RNA,尤其是微小RNA,在淋巴瘤发生中发挥关键调控作用。采用游离DNA(cfDNA)和循环肿瘤DNA(ctDNA)的液体活检等诊断创新,已提升早期检出、疾病监测和预后判断能力。
同时,分子生物标志物及新型分类方法改善了风险评估并指导治疗决策。治疗方式已超越传统化疗和放疗。单克隆抗体、激酶抑制剂、双特异性抗体及CAR-T 细胞疗法等靶向治疗,尤其在复发或难治病例中显示出良好前景。干细胞移植仍是部分患者的重要选择。
此外,靶向表观遗传机制和肿瘤血管生成的新型药物正在积极研究。本综述强调显著进展及持续挑战,如治疗耐药和不良反应。将分子诊断与精准靶向及免疫疗法相结合,是推进个体化照护的关键。未来研究应更好地表征肿瘤异质性并优化治疗策略,以改善B细胞淋巴瘤患者结局。
B-cell lymphomas (BCL) represent a heterogeneous group of blood cancers originating from B-lymphocytes, characterized by diverse clinical manifestations and molecular characteristics. This review highlights recent progress in understanding their pathogenesis, diagnostic approach advancements, and therapeutic strategies developments.
Key genetic alterations such as chromosomal translocations (e. g. , t(14;18), MYC rearrangements), mutations in tumor suppressor genes like TP53, and disruptions in critical signaling pathways including B-cell receptor (BCR), NF- B, PI3K/AKT, and JAK/STAT are central to disease development.
Additionally, non-coding RNAs, especially microRNAs, play crucial regulatory roles in lymphomagenesis. Innovations in diagnostics, such as liquid biopsy technologies using cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), have enhanced early detection, disease monitoring, and prognostication. Concurrently, molecular biomarkers and emerging classifiers improve risk assessment and guide treatment decisions.
Treatment approaches have evolved beyond traditional chemotherapy and radiotherapy. Targeted therapies such as monoclonal antibodies, kinase inhibitors, bispecific antibodies, and CAR-T cell therapies have shown particular promise in relapsed or refractory cases. Stem cell transplantation remains a valuable option for select patients.
Additionally, novel agents targeting epigenetic mechanisms and tumor angiogenesis are under active investigation. This review underscores both the significant advancements and ongoing challenges, such as therapy resistance and adverse effects. The integration of molecular diagnostics with precision-targeted and immune-based therapies is key to advancing personalized care. Future research should aim to characterize tumor heterogeneity better and optimize therapeutic strategies to improve outcomes for patients with B-cell lymphomas.
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