For one patient, next generation sequencing (NGS) was available for both original and recurrent tumor and did not reveal any major differences in the genetics of original tumor and distant recurrent tumor other than temozolomide induced high tumor mutational burden in the distant recurrent tumor. Understanding risk factors for distant recurrence in MGMT promoter methylated high grade gliomas and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve outcomes.

1 year ago

Clinical • Tumor mutational burden

TMB (Tumor Mutational Burden) • MGMT (6-O-methylguanine-DNA methyltransferase)

TMB-H • IDH wild-type • MGMT mutation

temozolomide

1year

Unraveling the signaling mechanism behind astrocytoma and possible therapeutics strategies: A comprehensive review. (PubMed, Cancer Rep (Hoboken))

In conclusion, cellular and molecular signaling is directly associated with the development of astrocytoma, and a combination of conventional and alternative therapies can improve the malignancy of cancer patients.

1 year ago

Review • Journal

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATRX (ATRX Chromatin Remodeler) • KIAA1549

TP53 mutation • BRAF V600E • BRAF V600 • PTEN mutation • ATRX mutation • MGMT mutation

1year

Genotyping, in silico screening and molecular dynamics simulation of SNPs of MGMT and ERCC1 gene in lung cancer patients treated with platinum-based doublet chemotherapy. (PubMed, J Biomol Struct Dyn)

Our study concludes that MGMT and ERCC1 polymorphisms are associated with decreased overall survival. Further, computational analysis of MGMT (rs12917) polymorphism revealed that mutated MGMT cannot bind properly to the DNA and hence cannot properly repair DNA, resulting in lower overall survival.Communicated by Ramaswamy H. Sarma.

1 year ago

Journal

ERCC1 (Excision repair cross-complementation group 1)

MGMT mutation

1year

Expression of TMEM59L associated with radiosensitive in glioblastoma. (PubMed, J Radiat Res)

Gene ontology and KEGG pathway analysis revealed that TMEM59L was closely related to the DNA damage repair and oxidative stress respond process. We speculated that the high expression of TMEM59L might enhance radiotherapy sensitivity by increasing ROS-induced DNA damage and inhibiting DNA damage repair process.

1 year ago

Journal

MGMT (6-O-methylguanine-DNA methyltransferase) • ZBTB7A (Zinc finger and BTB domain containing 7A) • GSN (Gelsolin)

MGMT mutation

over1year

Molecular markers impacting survival in patients receiving concurrent chemoradiation and Tumor-Treating Fields (TTF) in patients with newly diagnosed glioblastoma: secondary analysis of SPARE trial (AAN 2023)

Background SPARE trial (Scalp-sparing radiation with concurrent temozolomide (TMZ) and tumor treating fields; NCT03477110) is a single-arm pilot study that demonstrated the safety and feasibility of concurrent TTF with chemoradiation for newly diagnosed glioblastomas (GBM)...However, patients with TERT mutations showed improved OS. Due to the small sample size, further validation studies should be conducted.

over 1 year ago

Clinical

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase)

TP53 mutation • EGFR mutation • PTEN mutation • TERT mutation • IDH wild-type • EGFR mutation + TP53 mutation + PTEN mutation • MGMT mutation

temozolomide

almost2years

Epigenetic alterations in glioblastomas: diagnostic, prognostic and therapeutic relevance. (PubMed, Int J Cancer)

In detail, we will review the studies that have led to the identification of epigenetic signatures, IDH mutations, MGMT gene methylation, histone modification alterations, H3K27 mutations, and epitranscriptome landscapes of glioblastomas, in each case discussing the corresponding targeted therapies and their potential efficacy. Finally, we will emphasize how recent technological improvements permit to routinely investigate many glioblastoma epigenetic biomarkers in clinical practice, further enforcing the hope that personalized drugs, targeting specific epigenetic features, could be in future a therapeutic option for selected patients.

almost 2 years ago

Review • Journal

MGMT (6-O-methylguanine-DNA methyltransferase)

MGMT mutation

2years

Long-term outcome of patients with WHO grade 3 glioma treated with radiotherapy and temozolomide or radiotherapy alone (EANO 2022)

There have been several limitations in this study, for example the retrospectivesetting or the missing randomization of the patients. RT before 2005 resulted in the best long-term outcome, what has to be further investigated. However, RT/TMZ after 2005 showed asignificant benefit for the OS in the long term vs.

2 years ago

Clinical

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase)

MGMT mutation

temozolomide

over2years

Prognostic value of TERT mutation in adults with primary glioblastomas. Preliminary results (PubMed, Zh Vopr Neirokhir Im N N Burdenko)

Thus, the combined status of IDH1/2 and TERT mutations was a factor of better prognosis and can be proposed in clinical practice.

over 2 years ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase)

TERT mutation • MGMT mutation

over2years

Prognostic value of O -methylguanine-DNA methyltransferase methylation in isocitrate dehydrogenase mutant gliomas. (PubMed, Neurooncol Adv)

MGMT promoter methylation is associated with better OS and PFS for IDH mutant GBM. MGMT promoter methylation testing for other IDH mutant glioma subtypes may not provide additional information on prognostication.

over 2 years ago

Journal

MGMT (6-O-methylguanine-DNA methyltransferase)

MGMT promoter methylation • IDH wild-type • MGMT mutation

over2years

Reclassification of Glioblastoma Multiforme According to the 2021 World Health Organization Classification of Central Nervous System Tumors: A Single Institution Report and Practical Significance. (PubMed, Cureus)

Based on their significantly more favorable prognosis, the reclassification of IDH mutant forms of astrocytomas has had little epidemiological impact on this relatively common malignancy but has significantly underlined the dismal prognosis. The changes have also led to MGMT promoter methylation status being the only significant prognostic factor for patient survival in clinical use, based on its prediction for response to temozolomide therapy in this nosological unit clinically presenting when it has already reached immense size.

over 2 years ago

Journal

MGMT (6-O-methylguanine-DNA methyltransferase)

MGMT promoter methylation • MGMT mutation

temozolomide

almost3years

Trans-Sulcal Parafascicular Port-Based Resection of a Subcortical Occipital High-Grade Glioma: 2-Dimensional Operative Video. (PubMed, Oper Neurosurg (Hagerstown))

The participants and any identifiable individuals consented to the publication of their image. Images at 3:50 used with permission from Nico Corporation.

almost 3 years ago

Journal • Video

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase)

IDH1 mutation • MGMT mutation

3years

Phase 1 Clinical Trial of Oncolytic Viral Immunotherapy with CAN-2409 + Valacyclovir in Combination with Nivolumab and Standard of Care (SOC) in Newly Diagnosed High-Grade Glioma (HGG) (SNO 2021)

Temozolomide is administered to MGMT-methylation positive patients only. CONCLUSIONS The combination of CAN-2409 + nivolumab + SOC was well tolerated. Clinical follow-up and extensive biomarker analyses will provide a better understanding of the therapeutic potential of this approach.

3 years ago

Clinical • P1 data • Combination therapy • Oncolytic virus • PD(L)-1 Biomarker • IO biomarker

MGMT (6-O-methylguanine-DNA methyltransferase)

MGMT mutation

Opdivo (nivolumab) • temozolomide • ProstAtak (aglatimagene besadenovec) • valacyclovir

3years

[VIRTUAL] The Relationship Between Glioblastoma IDH Mutation and MGMT Methylation Status and Functional Gains During Inpatient Rehabilitation (AAPMR 2021)

The presence of certain molecular markers of GBM was associated with changes in FIM at discharge from the IRF. Though low in incidence, IDH-mutant GBM status was associated with greater functional gains. The exact mechanism requires further delineation.

3 years ago

Clinical

MGMT (6-O-methylguanine-DNA methyltransferase)

MGMT promoter methylation • MGMT mutation

3years

[VIRTUAL] A Randomized Trial of Short-Course vs. Conventional Radiotherapy With Concomitant and Adjuvant Temozolomide in Patients 18 to 70 Years of Age With Glioblastoma (ASTRO 2021)

The short-course RT regimen used in this trial was not inferior to conventional RT and was not associated with increased toxicity or reduced quality of life. Short-course RT is more convenient for patients and may be recommended as a treatment option for patients 70 years old or younger with newly diagnosed glioblastoma.

3 years ago

Clinical

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase)

IDH1 mutation • MGMT mutation

temozolomide

3years

A Randomized Trial of Short-Course Versus Conventional Radiotherapy With Concomitant and Adjuvant Temozolomide in Patients 18 to 70 Years of Age With Glioblastoma. (PubMed, Int J Radiat Oncol Biol Phys)

3 years ago

Clinical • Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase)

IDH1 mutation • MGMT mutation

temozolomide

over3years

Clinical and Genetic Features of Brainstem Glioma in Adults: A Report of 50 Cases in a Single Center. (PubMed, J Clin Neurol)

Adult BSGs showed different molecular genetic characteristics, but also resembled supratentorial gliomas in their clinical features associated with oncological outcomes.

over 3 years ago

Clinical • Journal

MGMT (6-O-methylguanine-DNA methyltransferase) • ATRX (ATRX Chromatin Remodeler)

MGMT promoter methylation • MGMT mutation

temozolomide

over3years

[VIRTUAL] A second hit by senolytic drug enhances zinc-alkylating agent cytotoxicity in pediatric glioblastoma (AACR 2021)

Our results suggest that zinc may serve as a potentiator of alkylating agents therapy in pediatric GB patients and using a second hit with senolytic drug in some cases may be even more beneficial.

over 3 years ago

Clinical

TP53 (Tumor protein P53) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)

TP53 mutation • MGMT mutation

over3years

Risk of Venous Thromboembolism in Grade II-IV Gliomas as a Function of Molecular Subtype. (PubMed, Neurology)

Patients with LGG have a higher VTE risk compared to the general population, which is decreased, but not eliminated, in the presence of an IDH mutation. MGMT promoter methylation in GBM does not affect the incidence of VTE.

over 3 years ago

Retrospective data • Journal

MGMT (6-O-methylguanine-DNA methyltransferase)

MGMT promoter methylation • MGMT mutation

almost5years

A Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma (Toca 6) (clinicaltrials.gov)

P1b, N=21, Terminated, Tocagen Inc. | N=30 --> 21 | Active, not recruiting --> Terminated; Sponsor decision

almost 5 years ago

Clinical • Enrollment change • Trial termination

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KDR (Kinase insert domain receptor) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • PTCH1 (Patched 1) • MSH6 (MutS homolog 6) • CDK12 (Cyclin dependent kinase 12) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • NOTCH2 (Notch 2) • KDM6A (Lysine Demethylase 6A) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) • STAG2 (Stromal Antigen 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • SOX9 (SRY-Box Transcription Factor 9) • DICER1 (Dicer 1 Ribonuclease III) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CHD4 (Chromodomain Helicase DNA Binding Protein 4) • GATA3 (GATA binding protein 3)

IDH1 mutation • KEAP1 mutation • MGMT promoter methylation • PTCH1 mutation • STAG2 mutation • MGMT mutation

vocimagene amiretrorepvec/extended release flucytosine (DB107)