泛素-蛋白酶体系统和自噬-溶酶体途径在多形性胶质母细胞瘤中的作用及药物研发进展

多形性胶质母细胞瘤是成年人最为常见，且恶性程度最高的原发性颅内肿瘤，约占颅脑肿瘤的30%～50%，复发率居颅内肿瘤首位，目前尚无有效的治疗药物。多形性胶质母细胞瘤的病因及发病机制尚未完全明确，但是越来越多的证据表明泛素-蛋白酶体系统和自噬-溶酶体途径参与了多形性胶质母细胞瘤的发生和发展，且2种调控途径存在的相互作用，促进了多形性胶质母细胞瘤的发生与耐药，二者可能是该疾病潜在的治疗靶点。然而，尽管国内外学者对泛素-蛋白酶体系统和自噬-溶酶体途径的生理和病理生理作用的认识已有了巨大发展，但是泛素-蛋白酶体系统和自噬-溶酶体途径抑制剂的研发和临床开发仍然面临挑战。综述了近年来泛素-蛋白酶体系统和自噬-溶酶体途径在多形性胶质母细胞瘤中的作用研究进展，并进一步探讨了以泛素-蛋白酶体系统和自噬-溶酶体途径为治疗靶点的药物研发最新进展，为多形性胶质母细胞瘤提供潜在药物靶点与治疗选择。

The Role of Ubiquitin-Proteasome System and Autophagy-Lysosome Pathway in Glioblastoma and their Research Progress in Drug Development

Glioblastoma multiforme (GBM) is the most common and most malignant primary intracranial tumor in adults, accounting for about 30% to 50% of cranial tumors, with the recurrence rate ranking first in intracranial tumors and currently still no effective treatment.Though its etiology and pathogenesis are still not fully understood, there is increasing evidence that dysfunction of the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathway (ALP) is involved in the development and progression of GBM.Besides, the interaction between the two regulatory pathways promotes the occurrence and drug resistance of GBM, so both may be potential therapeutic targets of GBM.However, despite significant advances in the understanding of the physiological and pathophysiological roles of UPS and ALP in GBM, the drug development and clinical application of UPS and ALP inhibitors still remain challenging.In this paper, the recent progress of research on the role of UPS and ALP in GBM are reviewed, and the latest development of drugs targeting UPS and ALP for the treatment of GBM are further discussed, so as to provide potential targets and more therapeutic options for GBM.