Glioblastoma multiforme (GBM) is one of the most common and malignant form of adult brain tumor with a high mortality rate and dismal prognosis. The present standard treatment comprising surgical resection followed by radiation and chemotherapy using temozolomide can broaden patient's survival to some extent. However, the advantages are not palliative due to the development of resistance to the drug and tumor recurrence following the multimodal treatment approaches due to both intra‐ and intertumoral heterogeneity of GBM. One of the major contributors to temozolomide resistance is O⁶‐methylguanine‐DNA methyltransferase. Furthermore, deficiency of mismatch repair, base excision repair, and cytoprotective autophagy adds to temozolomide obstruction. Rising proof additionally showed that a small population of cells displaying certain stem cell markers, known as glioma stem cells, adds on to the resistance and tumor progression. Collectively, these findings necessitate the discovery of novel therapeutic avenues for treating glioblastoma. As of late, after understanding the pathophysiology and biology of GBM, some novel therapeutic discoveries, such as drug repurposing, targeted molecules, immunotherapies, antimitotic therapies, and microRNAs, have been developed as new potential treatments for glioblastoma. To help illustrate, “what are the mechanisms of resistance to temozolomide” and “what kind of alternative therapeutics can be suggested” with this fatal disease, a detailed history of these has been discussed in this review article, all with a hope to develop an effective treatment strategy for GBM.

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解开 GBM 的治疗策略：从长凳到床边及其他

多形性胶质母细胞瘤（GBM）是成人脑肿瘤中最常见和恶性的形式之一，死亡率高，预后差。目前的标准治疗包括手术切除，然后使用替莫唑胺进行放疗和化疗，可以在一定程度上扩大患者的生存期。然而，由于 GBM 的肿瘤内和肿瘤间异质性，在多模式治疗方法后对药物产生耐药性和肿瘤复发，这些优势并不是姑息性的。替莫唑胺耐药性的主要贡献者之一是 O ⁶-甲基鸟嘌呤-DNA甲基转移酶。此外，错配修复、碱基切除修复和细胞保护性自噬的缺乏增加了替莫唑胺的阻塞。越来越多的证据还表明，显示某些干细胞标志物（称为神经胶质瘤干细胞）的一小部分细胞会增加耐药性和肿瘤进展。总的来说，这些发现需要发现治疗胶质母细胞瘤的新治疗途径。最近，在了解 GBM 的病理生理学和生物学后，一些新的治疗发现，如药物再利用、靶向分子、免疫疗法、抗有丝分裂疗法和 microRNA，已被开发为胶质母细胞瘤的新潜在治疗方法。为了帮助说明，