Molecular mechanisms in temozolomide-resistant glioblastoma

Lee, Sang Yup; Kitange, Gaspar J.

doi:10.1016/b978-0-12-821567-8.00029-4

Cited by 1 publication

(1 citation statement)

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“…EGFRvIII samples exhibited increased expression of CDK6 and ADAMTS9 , which are both implicated in temozolomide resistance. 29 This finding is interesting given that EGFRvIII expression may be related to temozolomide sensitivity. 30 To our knowledge, this represents the first study demonstrating a significant association between EGFRvIII expression and upregulation of resistance molecules such as CDK6 and ADAMTS9 , which creates an avenue for further investigation of combined influences of EGFRvIII, CDK6 upregulation, and ADAMTS9 upregulation related to temozolomide responsiveness.…”

Section: Discussionmentioning

confidence: 92%

Profiling the molecular and clinical landscape of glioblastoma utilizing the Oncology Research Information Exchange Network brain cancer database

Demetriou,

Chow,

Craig

et al. 2024

Neuro-Oncology Advances

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Background Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes. Methods Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test with Benjamini-Hochberg correction. Transcriptomic analyses utilized a student’s t-test with Benjamini-Hochberg correction. Expression fold changes were processed with Ingenuity Pathway Analysis to determine pathway-level alterations between groups. Results Key findings include an association of MUC17, SYNE1 and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher EGFR mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS >2 years; and two transcripts associated with OS <1 year. Conclusion Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.

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Section: Discussionmentioning

confidence: 92%