在胶质瘤治疗中应用“组合拳式”策略的研究

Research progress on"one-two punch"strategy in the therapy of glioma

胶质瘤(glioblastoma,GBM)起源于神经胶质细胞,尽可能完全手术切除后辅以放疗和化疗是当前的标准治疗方式。GBM在放化疗后不仅会加速细胞的死亡过程,还伴随着细胞衰老(cellular senescence)。衰老细胞会产生衰老相关的分泌表型(senescence-associated seretory phenotype,SASP),对肿瘤微环境产生双重影响。“组合拳式(one-two punch)”策略通过诱导肿瘤细胞衰老后特异性清除衰老细胞、抑制SASP分泌,这为肿瘤治疗提供了一个新的方向。本文就肿瘤衰老细胞和SASP的产生机制、抗衰老药物清除衰老细胞,以及目前采取“组合拳式”策略治疗GBM的情况进行综述。

Glioblastoma(GBM)originates from glial cells,and complete surgical resection followed by radiotherapy and chemotherapy is the current standard treatment.However,gliomas are subjected to not only accelerated cell death after radiotherapy and chemotherapy but also cellular senescence.Senescent cells produce a senescence-associated secretory phenotype(SASP),which has a dual effect on the tumor microenvironment.The"one-two punch"strategy of specifically eliminating senescent cells and inhibiting SASP-derived secretions provides a new direction for tumor therapy.In this article,we review the mechanisms that mediate tumor cellular senescence and SASP,the elimination of senescent cells by senolytics for SASP inhibition,and the current situation of the"one-two punch"strategy for the treatment of glioma.