Tirrò Elena, Massimino Michele, Romano Chiara, Martorana Federica, Pennisi Maria Stella, Stella Stefania, Pavone Giuliana, Di Gregorio Sandra, Puma Adriana, Tomarchio Cristina, Vitale Silvia Rita, Manzella Livia, Vigneri Paolo
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Center of Experimental Oncology and Hematology, A.O.U. Policlinico "G. Rodolico-San Marco", Catania, Italy.
Front Oncol. 2021 Feb 2;10:612385. doi: 10.3389/fonc.2020.612385. eCollection 2020.
Glioblastoma multiforme (GBM) is the most common primary brain malignancy and is often resistant to conventional treatments due to its extensive cellular heterogeneity. Thus, the overall survival of GBM patients remains extremely poor. Insulin-like growth factor (IGF) signaling entails a complex system that is a key regulator of cell transformation, growth and cell-cycle progression. Hence, its deregulation is frequently involved in the development of several cancers, including brain malignancies. In GBM, differential expression of several IGF system components and alterations of this signaling axis are linked to significantly worse prognosis and reduced responsiveness to temozolomide, the most commonly used pharmacological agent for the treatment of the disease. In the present review we summarize the biological role of the IGF system in the pathogenesis of GBM and comprehensively discuss its clinical significance and contribution to the development of resistance to standard chemotherapy and experimental treatments.
多形性胶质母细胞瘤（GBM）是最常见的原发性脑恶性肿瘤，由于其广泛的细胞异质性，常常对传统治疗产生耐药性。因此，GBM患者的总体生存率仍然极低。胰岛素样生长因子（IGF）信号传导是一个复杂的系统，是细胞转化、生长和细胞周期进程的关键调节因子。因此，其失调经常与包括脑恶性肿瘤在内的多种癌症的发生发展有关。在GBM中，几种IGF系统成分的差异表达以及该信号轴的改变与显著更差的预后以及对替莫唑胺（治疗该疾病最常用的药物）反应性降低有关。在本综述中，我们总结了IGF系统在GBM发病机制中的生物学作用，并全面讨论了其临床意义以及对标准化疗和实验性治疗耐药性发展的影响。
