Neurosurgical Department, Clinical Emergency Hospital "Bagdasar-Arseni", Soseaua Berceni 12, 041915 Bucharest, Romania.
Neuromuscular Rehabilitation Department, Clinical Emergency Hospital "Bagdasar-Arseni", Soseaua Berceni 12, 041915 Bucharest, Romania.
Int J Mol Sci. 2023 Jul 5;24(13):11110. doi: 10.3390/ijms241311110.
Despite all of the progress in understanding its molecular biology and pathogenesis, glioblastoma (GBM) is one of the most aggressive types of cancers, and without an efficient treatment modality at the moment, it remains largely incurable. Nowadays, one of the most frequently studied molecules with important implications in the pathogenesis of the classical subtype of GBM is the epidermal growth factor receptor (EGFR). Although many clinical trials aiming to study EGFR targeted therapies have been performed, none of them have reported promising clinical results when used in glioma patients. The resistance of GBM to these therapies was proven to be both acquired and innate, and it seems to be influenced by a cumulus of factors such as ineffective blood-brain barrier penetration, mutations, heterogeneity and compensatory signaling pathways. Recently, it was shown that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. It seems imperative to understand how the EGFR signaling pathways function and how they interconnect with other pathways. Furthermore, it is important to identify the mechanisms of drug resistance and to develop better tailored therapeutic agents.
尽管在了解其分子生物学和发病机制方面已经取得了所有进展，但胶质母细胞瘤 (GBM) 仍然是最具侵袭性的癌症之一，目前还没有有效的治疗方法，因此仍然基本上无法治愈。如今，在经典型 GBM 的发病机制中具有重要意义的最常研究的分子之一是表皮生长因子受体 (EGFR)。尽管已经进行了许多旨在研究 EGFR 靶向治疗的临床试验，但当将它们用于 glioma 患者时，没有一种报告了有前途的临床结果。GBM 对这些治疗的耐药性已被证明是获得性和内在性的，并且似乎受到诸如血脑屏障通透性降低、突变、异质性和补偿性信号通路等因素的累积影响。最近表明，EGFR 在癌细胞中具有激酶非依赖性 (KID) 促生存功能。了解 EGFR 信号通路的功能以及它们如何与其他通路相互作用至关重要。此外，确定耐药机制并开发更好的靶向治疗药物非常重要。
