Putavet Diana A, de Keizer Peter L J
Center for Molecular Medicine, Division LAB, University Medical Center Utrecht, 3584CG Utrecht, The Netherlands.
Cancers (Basel). 2021 Mar 29;13(7):1560. doi: 10.3390/cancers13071560.
With a dismally low median survival of less than two years after diagnosis, Glioblastoma (GBM) is the most lethal type of brain cancer. The standard-of-care of surgical resection, followed by DNA-damaging chemo-/radiotherapy, is often non-curative. In part, this is because individual cells close to the resection border remain alive and eventually undergo renewed proliferation. These residual, therapy-resistant cells lead to rapid recurrence, against which no effective treatment exists to date. Thus, new experimental approaches need to be developed against residual disease to prevent GBM survival and recurrence. Cellular senescence is an attractive area for the development of such new approaches. Senescence can occur in healthy cells when they are irreparably damaged. Senescent cells develop a chronic secretory phenotype that is generally considered pro-tumorigenic and pro-migratory. Age is a negative prognostic factor for GBM stage, and, with age, senescence steadily increases. Moreover, chemo-/radiotherapy can provide an additional increase in senescence close to the tumor. In light of this, we will review the importance of senescence in the tumor-supportive brain parenchyma, focusing on the invasion and growth of GBM in residual disease. We will propose a future direction on the application of anti-senescence therapies against recurrent GBM.
胶质母细胞瘤（GBM）是最致命的脑癌类型，诊断后的中位生存期低至不到两年，令人沮丧。标准治疗方法是手术切除，然后进行破坏DNA的化学/放射治疗，但往往无法治愈。部分原因是靠近切除边界的单个细胞仍存活并最终重新增殖。这些残留的、对治疗有抗性的细胞导致快速复发，迄今为止尚无有效的治疗方法。因此，需要开发针对残留疾病的新实验方法，以防止GBM存活和复发。细胞衰老对于开发此类新方法来说是一个有吸引力的领域。当健康细胞受到无法修复的损伤时，就会发生衰老。衰老细胞会形成一种慢性分泌表型，通常被认为具有促肿瘤发生和促迁移作用。年龄是GBM分期的一个负面预后因素，并且随着年龄增长，衰老会稳步增加。此外，化学/放射治疗可使肿瘤附近的衰老进一步增加。有鉴于此，我们将综述衰老在支持肿瘤的脑实质中的重要性，重点关注GBM在残留疾病中的侵袭和生长。我们将提出针对复发性GBM应用抗衰老疗法的未来方向。
