间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Current Progress on Predictive Biomarkers for Response to Immune Checkpoint Inhibitors in Gastric Cancer: How to Maximize the Immunotherapeutic Benefit?
Current Progress on Predictive Biomarkers for Response to Immune Checkpoint Inhibitors in Gastric Cancer: How to Maximize the Immunotherapeutic Benefit?
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胃癌是全球第五大常见癌症,也是第四大癌症死亡原因。诊断延迟以及显著的组织学和分子变异增加了治疗的复杂性和挑战。药物治疗长期以来是以5-氟尿嘧啶为基础的系统性化疗,是晚期胃癌的主要治疗手段。曲妥珠单抗和程序性细胞死亡1(PD-1)抑制剂改变了治疗格局,显著延长了转移性胃癌患者的生存期。然而,研究表明免疫治疗仅对部分个体有益。生物标志物,如程序性细胞死亡配体1(PD-L1)、微卫星不稳定性(MSI)和肿瘤突变负荷(TMB),已在大量研究中被证明与免疫疗效相关,并越来越多地用于筛选最可能对免疫治疗产生应答的患者。肠道微生物、POLE/POLD1和NOTCH4等基因突变、肿瘤淋巴浸润细胞(TILs)以及其他新型生物标志物有潜力成为新的预测因子。胃癌免疫治疗的前景应以生物标志物驱动的精准管理范式为指导,多维或动态标志物检测可能是未来的方向。
Gastric cancer is the fifth most prevalent cancer and the fourth leading cause of cancer death globally. Delayed diagnosis and pronounced histological and molecular variations increase the complexity and challenge of treatment.
Pharmacotherapy, which for a long time was systemic chemotherapy based on 5-fluorouracil, is the mainstay of management for advanced gastric cancer. Trastuzumab and programmed cell death 1 (PD-1) inhibitors have altered the therapeutic landscape, contributing to noticeably prolonged survivorship in patients with metastatic gastric cancer.
However, research has revealed that immunotherapy is only beneficial to some individuals. Biomarkers, such as programmed cell death ligand 1 (PD-L1), microsatellite instability (MSI), and tumor mutational load (TMB), have been shown to correlate with immune efficacy in numerous studies and are increasingly employed for the selection of patients most likely to respond to immunotherapy.
Gut microorganisms, genetic mutations like POLE/POLD1 and NOTCH4, tumor lymphoid infiltrating cells (TILs), and other novel biomarkers have the potential to develop into new predictors. Prospective immunotherapy for gastric cancer should be guided by a biomarker-driven precision management paradigm, and multidimensional or dynamic marker testing could be the way to go.
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