Up-regulation of MSH6 is associated with temozolomide resistance in human glioblastoma

DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance

“…Additional studies are necessary to better describe their roles in GBM biology and potential enrollment as biomarkers. In agreement, a study including 539 GBM cases identified and validated a gene expression signature including 15 key DNA repair genes significantly correlated to prognosis, and five of them (CDK7, DDB2, RNH1, 4 de Sousa et al Hunter et al, 2006;Maxwell et al, 2008;Yip et al, 2009;Sun et al, 2018 *This table shows only the biomarkers discussed throughout the review. Please refer to the text for further information.…”

“…Additionally, clinical data showed the presence of MSH6 mutations in GBM specimens after TMZ therapy but not in pre-treatment sam-ples, suggesting that these changes results from CT and may contribute to recurrence (Hunter et al, 2006;Yip et al, 2009). However, other studies suggest that MMR deficiency does not mediate clinical resistance to temozolomide (Maxwell et al, 2008) and that the upregulation of MSH6 could be associated with resistance, opposing the relationship between MMR and TMZ resistance (Sun et al, 2018). Thus, further studies are necessary to better elucidate the complex network involved in DNA repair and its relationship TMZ resistance.…”

Biomarker-guided implementation of the old drug temozolomide as a novel treatment option for patients with metastatic colorectal cancer

“…Notably, C > T transitions are frequently found in MSI-high cancers characterized by small insertions and deletions at mono/polynucleotide repeats [75]. In glioblastoma, the inactivation of MMR-related genes has been reported at the time disease recurrence after initial temozolomide-based treatment [76][77][78][79][80] (Supplementary Table S2). Overall, the prevalence of glioblastoma relapses with hypermutated phenotype due to MMR inactivation after temozolomide treatment is about 10-20% [81].…”

Amlexanox enhances temozolomide-induced anti-tumor effects in human glioblastoma cells by inhibiting IKBKE and the Akt-mTOR signaling pathway

“…The overexpression of O 6 -methylguanine-DNA-methyltransferase (MGMT) is one of the main resistance mechanisms for repairing O 6 methylguanine, which is an important TMZ-induced lesion resulting in breakage of DNA double-strand and subsequent apoptosis [6,5]. In addition, immune escape after TMZ treatment [25], dysfunction of the DNA mismatch repair (MMR) system [1], as well as abnormal expression of nuclear factor erythroid 2related factor 2 (Nrf2) [26] and high expression of ATP-binding cassette (ABC) membrane transporters [2], were also demonstrated to be involved in resistance development. However, what greatly interested us is the activation of AKT, which is involved various cellular processes, such as proliferation, cell growth and survival [14].…”

“…Glioblastoma multiforme (GBM), which accounts for more than 60-70% of all gliomas, is the most aggressive and most deadly primary brain tumor in adults [1,2]. Over the past decades, although there has been progress regarding human GBM treatment, currently including maximal surgical resection followed by chemotherapy and/or radiotherapy, the prognosis of patients diagnosed with GBM remains extremely grim, with a median survival of approximately 14.6 months and a 5-year survival rate of only 9.8% [3,4].…”