Glioblastoma (GBM), the most common and lethal primary brain tumor in adults, requires multi-treatment intervention which unfortunately barely shifts the needle in overall survival. The treatment options after diagnosis and surgical resection (if possible) include irradiation, temozolomide (TMZ) chemotherapy, and now Tumor Treating Fields (TTFields). TTFields are electric fields delivered locoregionally to the head/tumor via a wearable medical device (Optune®). Overall, the concomitant treatment of TTFields and TMZ target tumor cells but spare normal cell types in the brain. Here, we examine whether primary cilia, microtubule based ‘antennas’ found on both normal brain cells and GBM cells, play specific roles in sensitizing tumor cells to treatment. We discuss evidence supporting GBM cilia being exploited by tumor cells to promote their growth and treatment resistance. We review how primary cilia on normal brain and GBM cells are affected by GBM treatments as monotherapy or concomitant modalities. We also focus on latest findings indicating a differential regulation of GBM ciliogenesis by TTFields and TMZ. Future studies await arrival of intracranial TTFields models to determine if GBM cilia carry a prognostic capacity.


中文翻译：

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纤毛处于肿瘤治疗领域和化疗的十字路口

胶质母细胞瘤 (GBM) 是成人中最常见和致命的原发性脑肿瘤，需要多种治疗干预，不幸的是，这几乎不能改变总体生存率。诊断和手术切除（如果可能）后的治疗选择包括放疗、替莫唑胺 (TMZ) 化疗，以及现在的肿瘤电场治疗 (TTFields)。TTFields 是通过可穿戴医疗设备 (Optune®) 局部传送到头部/肿瘤的电场。总的来说，TTFields 和 TMZ 的联合治疗靶向肿瘤细胞，但不影响大脑中的正常细胞类型。在这里，我们检查在正常脑细胞和 GBM 细胞上发现的初级纤毛、基于微管的“天线”是否在使肿瘤细胞对治疗敏感中发挥特定作用。我们讨论了支持 GBM 纤毛被肿瘤细胞利用以促进其生长和治疗耐药性的证据。我们回顾了正常大脑和 GBM 细胞上的原发性纤毛如何受到 GBM 治疗作为单一疗法或伴随疗法的影响。我们还关注最新发现，表明 TTFields 和 TMZ 对 GBM 纤毛发生的不同调节。未来的研究等待颅内 TTFields 模型的到来，以确定 GBM 纤毛是否具有预后能力。