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第44卷第5期
               ·694 ·                            南 京    医 科 大 学 学         报                        2024年5月


              提供了与患者肿瘤高度相似的研究工具,在GBM化                                Regorafenib compared with lomustine in patients with re⁃
              疗耐药研究中起着关键作用。一方面,GBO模型为                                lapsed glioblastoma(REGOMA):a multicentre,open⁃la⁃
              个体化治疗提供了高通量的药物筛选和验证平台,                                 bel,randomised,controlled,phase 2 trial[J]. Lancet On⁃
              用于精准确定个体化辅助治疗药物,提高复发患者的                                col,2019,20(1):110-119
                                                                [6] REARDON D A,BRANDES A A,OMURO A,et al.
              生存率   [77-78] ;另一方面,GBO模型能够保留患者肿瘤
                                                                     Effect of nivolumab vs bevacizumab in patients with re⁃
              中的相关生物标志物,预测患者对治疗的反应                     [79-80] 。
                                                                     current glioblastoma:the checkmate 143 phase 3 random⁃
              例如,研究人员通过 GBO 进行前瞻性药物筛选,预                              ized clinical trial[J]. JAMA Oncol,2020,6(7):1003-
              测患者对厄洛替尼、维罗非尼和依维莫司的响应                                  1010
              性,依据预测结果选择使用依维莫司并在患者中取                            [7] TSIEN C I,PUGH S L,DICKER A P,et al. NRG oncolo⁃
              得了较好的疗效 。                                              gy/RTOG1205:a randomized phase Ⅱ trial of concurrent
                            [81]
                                                                     bevacizumab and reirradiation versus bevacizumab alone
              4  未来展望                                                as treatment for recurrent glioblastoma[J]. J Clin Oncol,
                                                                     2023,41(6):1285-1295
                  尽管 GBM 的治疗方法在过去几年中取得了一
                                                                [8] LIM M,WELLER M,IDBAIH A,et al. Phase Ⅲ trial of
              定的进展,但患者 5 年生存率仍然很低,并且复发
                                                                     chemoradiotherapy with temozolomide plus nivolumab or
              GBM 患者通常比初发患者表现出更加复杂的分子
                                                                     placebo for newly diagnosed glioblastoma with methylated
              特征和通路异常,使得治疗变得尤为困难。越来越                                 MGMT promoter[J]. Neuro ⁃ oncology,2022,24(11):
              多的研究证明 TMZ 耐药是由多个分子事件共同作                               1935-1949
              用的结果。这些事件在不同层面发挥作用,导致单                            [9] OMURO A,BRANDES A A,CARPENTIER A F,et al.
              一疗法很难为患者带来显著益处。因此,多模式治                                 Radiotherapy combined with nivolumab or temozolomide
              疗方法,即结合多种不同治疗手段开发的新型治疗                                 for newly diagnosed glioblastoma with unmethylated
              策略正在 GBM 治疗中显示出潜力,包括靶向疗法、                              MGMT promoter:an international randomized phase Ⅲ
                                                                     trial[J]. Neuro Oncol,2023,25(1):123-134
              免疫治疗等。随着科学技术的进步和对 GBM 生物
                                                                [10]TOMAR M S,KUMAR A,SRIVASTAVA C,et al. Eluci⁃
              学的深入了解,未来的治疗策略将更加多元化,更
                                                                     dating the mechanisms of temozolomide resistance in glio⁃
              加精准地针对肿瘤的异质性和复杂性进行个体化
                                                                     mas and the strategies to overcome the resistance[J]. Bio⁃
              治疗,延缓甚至阻断 TMZ耐药,提高治疗效果,延长                              chim Biophys Acta Rev Cancer,2021,1876(2):188616
              患者的生存期,为患者带来新的希望。                                 [11]OLDRINI B,VAQUERO ⁃ SIGUERO N,MU Q H,et al.
                                                                     MGMT genomic rearrangements contribute to chemothera⁃
             [参考文献]
                                                                     py resistance in gliomas[J]. Nat Commun,2020,11(1):
             [1] WELLER M,VAN DEN BENT M,PREUSSER M,et al.
                                                                     3883
                   EANO guidelines on the diagnosis and treatment of dif⁃
                                                                [12]WICK W,PLATTEN M,MEISNER C,et al. Temozolo⁃
                   fuse gliomas of adulthood[J]. Nat Rev Clin Oncol,2021,
                                                                     mide chemotherapy alone versus radiotherapy alone for
                   18(3):170-186
                                                                     malignant astrocytoma in the elderly:the NOA ⁃ 08 ran⁃
             [2] STUPP R,MASON W P,VAN DEN BENT M J,et al. Ra⁃       domised,phase 3 trial[J]. Lancet Oncol,2012,13(7):
                   diotherapy plus concomitant and adjuvant temozolomide
                                                                     707-715
                   for glioblastoma[J]. N Engl J Med,2005,352(10):987-
                                                                [13]BRANDES A A ,FRANCESCHI E ,TOSONI A ,et al.
                   996
                                                                     O(6)⁃methylguanine DNA⁃methyltransferase methylation
             [3] MEDICAL RESEARCH COUNCIL BRAIN TUMOR
                                                                     status can change between first surgery for newly ding⁃
                   WORKING PARTY. Randomized trial of procarbazine,
                                                                     nosed glioblastoma and second sugery for recurrence:clini⁃
                   lomustine,and vincristine in the adjuvant treatment of high⁃
                                                                     cal implications[J]. Neuro Oncol,2010,12(3):283-288
                   grade astrocytoma:a medical research council trial[J]. J
                                                                [14]GAN T,WANG Y,XIE M Y,et al. MEX3A impairs DNA
                   Clin Oncol,2001,19(2):509-518
                                                                     mismatch repair signaling and mediates acquired temo⁃
             [4] KIM S H,YOO H,CHANG J H,et al. Procarbazine and     zolomide resistance in glioblastoma[J]. Cancer Res,
                   CCNU chemotherapy for recurrent glioblastoma with
                                                                     2022,82(22):4234-4246
                   MGMT promoter methylation[J]. J Korean Med Sci,  [15]FELSBERG J,THON N,EIGENBROD S,et al. Promoter
                   2018,33(24):167                                   methylation and expression of MGMT and the DNA mis⁃
             [5] LOMBARDI G,DE SALVO G L,BRANDES A A,et al.          match repair genes MLH1,MSH2,MSH6 and PMS2 in
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