Abstract:
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.
摘要:
脑膜瘤是中枢神经系统中最常见的原发性肿瘤。它们通常遵循良性的过程,通过手术干预,I级病变的预后良好。虽然放疗是复发的好选择,进步,或者不能手术的肿瘤,替代疗法非常有限。mTOR是一种蛋白质复合物,具有增加的作为癌症靶标的治疗潜力。当前对mTOR途径的理解在脑膜瘤的发展中涉及到mTOR途径。其激活强烈依赖于PI3K/Akt信号传导和merlin蛋白。这两种因素在脑膜瘤细胞中通常都有缺陷,这表明它们可能在肿瘤生长中发挥作用。此外,关于分子肿瘤发生,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,瘤形成的重要组成部分。最近的临床试验已经研究了用于mTOR抑制的新型化学治疗剂,在耐药或复发性脑膜瘤中显示出有希望的结果。