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Genotoxic therapy and resistance mechanism in gliomas
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2021-06-23 , DOI: 10.1016/j.pharmthera.2021.107922
Fengchao Lang 1 , Yang Liu 1 , Fu-Ju Chou 1 , Chunzhang Yang 1
Affiliation  

Glioma is one of the most common and lethal brain tumors. Surgical resection followed by radiotherapy plus chemotherapy is the current standard of care for patients with glioma. The existence of resistance to genotoxic therapy, as well as the nature of tumor heterogeneity greatly limits the efficacy of glioma therapy. DNA damage repair pathways play essential roles in many aspects of glioma biology such as cancer progression, therapy resistance, and tumor relapse. O6-methylguanine-DNA methyltransferase (MGMT) repairs the cytotoxic DNA lesion generated by temozolomide (TMZ), considered as the main mechanism of drug resistance. In addition, mismatch repair, base excision repair, and homologous recombination DNA repair also play pivotal roles in treatment resistance as well. Furthermore, cellular mechanisms, such as cancer stem cells, evasion from apoptosis, and metabolic reprogramming, also contribute to TMZ resistance in gliomas. Investigations over the past two decades have revealed comprehensive mechanisms of glioma therapy resistance, which has led to the development of novel therapeutic strategies and targeting molecules.



中文翻译:

胶质瘤的基因毒性治疗和耐药机制

神经胶质瘤是最常见和致命的脑肿瘤之一。手术切除后放疗加化疗是神经胶质瘤患者目前的标准治疗。对基因毒性治疗耐药性的存在,以及肿瘤异质性的性质,极大地限制了神经胶质瘤治疗的疗效。DNA 损伤修复途径在神经胶质瘤生物学的许多方面发挥着重要作用,例如癌症进展、治疗耐药性和肿瘤复发。O6-甲基鸟嘌呤-DNA 甲基转移酶 (MGMT) 修复由替莫唑胺 (TMZ) 产生的细胞毒性 DNA 损伤,被认为是耐药的主要机制。此外,错配修复、碱基切除修复和同源重组 DNA 修复也在治疗耐药性中发挥关键作用。此外,细胞机制,如癌症干细胞,逃避细胞凋亡和代谢重编程也有助于神经胶质瘤中的 TMZ 抗性。过去二十年的研究揭示了神经胶质瘤治疗耐药的综合机制,这导致了新的治疗策略和靶向分子的发展。

更新日期:2021-06-25
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