Medical Faculty, Karol Marcinkowski University of Medical Sciences, Fredry 10, 61-701 Poznan, Poland.
Intraoperative Imaging Unit, Chair and Department of Neurosurgery and Neurotraumatology, Karol Marcinkowski University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznan, Poland.
Int J Mol Sci. 2022 Feb 10;23(4):1978. doi: 10.3390/ijms23041978.
Meningiomas are the most frequent primary tumors arising in the central nervous system. They typically follow a benign course, with an excellent prognosis for grade I lesions through surgical intervention. Although radiotherapy is a good option for recurrent, progressive, or inoperable tumors, alternative treatments are very limited. mTOR is a protein complex with increasing therapeutical potential as a target in cancer. The current understanding of the mTOR pathway heavily involves it in the development of meningioma. Its activation is strongly dependent on PI3K/Akt signaling and the merlin protein. Both factors are commonly defective in meningioma cells, which indicates their likely function in tumor growth. Furthermore, regarding molecular tumorigenesis, the kinase activity of the mTORC1 complex inhibits many components of the autophagosome, such as the ULK1 or Beclin complexes. mTOR contributes to redox homeostasis, a vital component of neoplasia. Recent clinical trials have investigated novel chemotherapeutic agents for mTOR inhibition, showing promising results in resistant or recurrent meningiomas.
脑膜瘤是中枢神经系统最常见的原发性肿瘤。它们通常呈良性病程，通过手术干预，I 级病变的预后极好。尽管放疗是复发性、进行性或不可手术肿瘤的良好选择，但替代治疗方法非常有限。mTOR 是一种蛋白复合物，作为癌症治疗靶点具有越来越大的治疗潜力。目前对 mTOR 通路的理解表明它在脑膜瘤的发生发展中起重要作用。其激活强烈依赖于 PI3K/Akt 信号通路和 Merlin 蛋白。这两个因素在脑膜瘤细胞中通常存在缺陷，表明它们可能在肿瘤生长中发挥作用。此外，就分子肿瘤发生而言，mTORC1 复合物的激酶活性抑制自噬体的许多成分，如 ULK1 或 Beclin 复合物。mTOR 有助于氧化还原稳态，这是肿瘤发生的一个重要组成部分。最近的临床试验研究了针对 mTOR 抑制的新型化疗药物，在耐药或复发性脑膜瘤中显示出有希望的结果。
