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    BIOMARKER:

    IDH wild-type

    i
    Other names: HEL-216, HEL-S-26, Epididymis Luminal Protein 216, Isocitrate Dehydrogenase 1 (NADP+), Epididymis Secretory Protein Li 26, IDH1, Isocitrate Dehydrogenase (NADP(+)) 1, Isocitrate Dehydrogenase 1 (NADP+), Soluble, IDH2, Isocitrate Dehydrogenase (NADP(+)) 2, Isocitrate Dehydrogenase (NADP(+)) 2, Mitochondrial, Isocitrate Dehydrogenase 2 (NADP+), Mitochondrial, Isocitrate Dehydrogenase [NADP], Mitochondrial, Oxalosuccinate Decarboxylase, NADP(+)-Specific ICDH, ICD-M, IDH, IDP, MNADP-IDH, D2HGA2, IDHM, IDPM
    Entrez ID:
    3417; 3418
    Related biomarkers:
    Expression
    Mutation
    Others
    27d
    Risk factors for and molecular pathology characteristics of systemic metastasis of adult cerebral glioblastoma: A pooled individual patient data analysis and systematic review. (PubMed, J Neurol Surg A Cent Eur Neurosurg)
    Conclusion In young adult GBM patients, especially those ≤ 40 years of age with long survival, attention should be given to the development of systemic metastases. Metastasis can be the result of multiclonal gene mutations, in which proliferation- and invasion-related gene changes, such as oncogene or tumor suppressor gene mutations and epithelial-mesenchymal transition-related genes, may play an important role in metastasis.
    Review • Journal
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • TERT (Telomerase Reverse Transcriptase)
    |
    TP53 mutation • PTEN mutation • RB1 mutation • TERT mutation • IDH wild-type • TERT promoter mutation
    29d
    Phase 2 Trial of Veliparib, Local Irradiation and Temozolomide in Patients with Newly Diagnosed High-Grade Glioma: A Children's Oncology Group Study. (PubMed, Neuro Oncol)
    Rapid central pathology review and molecular testing for eligibility was feasible. The protocol therapy including radiation, veliparib and temozolomide was well tolerated but failed to improve outcome compared to clinically and molecularly matched historical control cohorts treated with higher doses of alkylator chemotherapy.
    P2 data • Journal • PARP Biomarker
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • IDH wild-type
    |
    temozolomide • veliparib (ABT-888)
    29d
    Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses. (PubMed, Neuro Oncol)
    Glioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase)
    |
    CDKN2A deletion • CDKN2A mutation • TERT mutation • IDH wild-type • TERT promoter mutation
    |
    temozolomide
    30d
    Diffuse pediatric high-grade glioma of methylation-based RTK2A and RTK2B subclasses present distinct radiological and histomolecular features including Gliomatosis cerebri phenotype. (PubMed, Acta Neuropathol Commun)
    In conclusion, pedHGG-RTK2A/B tumors are characterized by highly diffuse-infiltrating growth patterns and specific radiological and histo-molecular features. By comprehensively characterizing methylation-based tumors, the chance to develop specific and effective therapy concepts for these detrimental tumors increases.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BCOR (BCL6 Corepressor) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • OLIG2 (Oligodendrocyte Transcription Factor 2)
    |
    EGFR expression • BCOR mutation • IDH wild-type
    1m
    NRG-BN010: Testing the Addition of the Immune Therapy Drugs, Tocilizumab and Atezolizumab, to Radiation Therapy for Recurrent Glioblastoma (clinicaltrials.gov)
    P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR (Epidermal growth factor receptor) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase)
    |
    EGFR amplification • TERT mutation • IDH wild-type • TERT promoter mutation
    |
    Tecentriq (atezolizumab) • Actemra IV (tocilizumab)
    1m
    A novel machine learning model integrating clinical and molecular data to predict response to second line treatment in recurrent IDHwtglioblastoma (AIOM 2024)
    Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas.
    Clinical • Machine learning
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • EGFR mutation • PTEN mutation • IDH wild-type • MTAP mutation
    |
    FoundationOne® CDx
    |
    Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)
    1m
    PTEN alteration as a predictor of second-line efficacy in patients with recurrent IDHwt-glioblastoma (rGBM) (AIOM 2024)
    Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of pTEN in these patient populations.
    Clinical
    |
    PTEN (Phosphatase and tensin homolog) • MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    PTEN mutation • IDH wild-type
    |
    FoundationOne® CDx
    |
    Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)
    1m
    Serum lactate dehydrogenase as a prognostic marker for treatment response in IDH wild-type glioblastoma patients undergoing stupp protocol. (PubMed, J Neurooncol)
    Elevated LDH levels before starting the Stupp protocol are clinically significant as they predict poorer overall survival and progression-free survival in glioblastoma patients and worse RR. Incorporating LDH measurements into treatment planning can help identify patients at higher risk of poor outcomes, allowing for more tailored and potentially aggressive treatment strategies to improve management and therapeutic responses in glioblastoma.
    Journal
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    LDH elevation • MGMT promoter methylation • LDH-L • IDH wild-type
    |
    temozolomide
    1m
    Identification of an Immune signature assisted prognosis, and immunotherapy prediction for IDH wildtype glioblastoma. (PubMed, J Cancer)
    Immune checkpoint genes correlation analysis showed that PD-L1 gene expression is closely related to risk score. Our study identifies a prognostic-associated risk model and provides a potential effective immunotherapy target for IDH-wildtype GBM patients.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • FMOD (Fibromodulin)
    |
    PD-L1 expression • IDH wild-type
    1m
    To Use or Not to Use: Temozolomide in Elderly Patients with IDH Wild-type MGMT Promoter Unmethylated Glioblastoma Treated with Radiotherapy. (PubMed, Cancer Res Treat)
    The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.
    Journal
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    temozolomide
    1m
    Spatial transcriptomics analysis identifies therapeutic targets in diffuse high-grade gliomas. (PubMed, Front Mol Neurosci)
    Spatial transcriptome analysis is one of the breakthroughs in the field of medical biotechnology as this can map the analytes such as RNA information in their physical location in tissue sections. Our findings illuminate previously unexplored spatial expression profiles of key biomarkers in diffuse high-grade glioma, offering novel insight for the development of therapeutic strategies in glioma.
    Journal
    |
    SPP1 (Secreted Phosphoprotein 1) • IGFBP2 (Insulin-like growth factor binding protein 2) • APOE (Apolipoprotein E) • HIPK2 (Homeodomain Interacting Protein Kinase 2) • S100A6 (S100 calcium binding protein A6) • SMOC1 (SPARC Related Modular Calcium Binding 1)
    |
    IDH wild-type
    1m
    IDH1/2 Mutations in Lung Cancer: A Closer Look at Their Incidence, Origin, and Clinical Characteristics (AMP 2024)
    IDH1/2 mutations are identified in a small subset of NSCLCs. Our findings suggest that >25% of these mutations are hematopoietic in origin with important implications for diagnosis and management of these patients. Among those with mutations arising from the lung neoplasm, IDH1/2 mutations were primarily seen in conjunction with another driver and were subclonal in nature, suggesting patterns of clonal heterogeneity and evolution.
    Clinical • Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    KRAS mutation • BRAF mutation • IDH wild-type • IDH1 R132 • IDH2 R140Q • IDH1 R132L • IDH2 R140 • IDH2 R172
    |
    MSK-IMPACT
    1m
    Detection of 1p/19q Co-deletion Using Hybridization-Capture-Based Targeted Next-Generation Sequencing (AMP 2024)
    Targeted hybridization-capture-based NGS assays can be a robust and reliable method for detecting 1p/19q co-deletion in gliomas. NGS methodologies provide enhanced resolution of copy number alterations but require a minimum tumor content.
    Next-generation sequencing
    |
    TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • IDH wild-type • IDH1 mutation + TP53 mutation
    |
    TruSight Oncology 500 Assay
    1m
    ACNS1721: Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations (clinicaltrials.gov)
    P2, N=38, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025
    Trial completion date
    |
    BRAF (B-raf proto-oncogene)
    |
    IDH wild-type
    |
    temozolomide • veliparib (ABT-888)
    1m
    NCI-2019-03057: Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation (clinicaltrials.gov)
    P2, N=14, Active, not recruiting, National Cancer Institute (NCI) | N=94 --> 14 | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Jan 2024
    Enrollment change • Trial completion date • Trial primary completion date
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH wild-type • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132L • IDH1 R132S • IDH1 R132V • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)
    1m
    CAN-201 NDG: Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma (clinicaltrials.gov)
    P1/2, N=18, Active, not recruiting, Cantex Pharmaceuticals | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    RAS wild-type • IDH wild-type
    |
    temozolomide • azeliragon (TTP488)
    1m
    A phase IIa clinical trial study on the efficacy and safety of bevacizumab combined with temozolomide concurrent radiotherapy followed by bevacizumab combined with temozolomide and anlotinib in the treatment of primary glioblastoma (ChiCTR2400091275)
    P2, N=40, Not yet recruiting, Affiliated Cancer Hospital of Shandong First Medical University; Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandon
    New P2 trial
    |
    IDH wild-type
    |
    Avastin (bevacizumab) • Focus V (anlotinib) • temozolomide
    1m
    Differences in gene expression, genome-wide methylation and metabolites in adult diffuse gliomas (SNO 2024)
    Consequently, we observed higher levels of uracil in tissue and CSF samples from patients with IDH wild-type gliomas. These data provide a framework to study the relationship between mutations, methylation, gene expression and metabolism in diffuse gliomas.
    Clinical
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH wild-type • UPP1 overexpression
    |
    nCounter® Metabolic Pathways Panel
    1m
    Current status of cancer genomic profiling (CGP) tests in brain tumor treatment - complementing brain tumor pathological diagnosis with CGP- (SNO 2024)
    Molecular diagnostics through CGP testing served as an aid in diagnosis according to WHO2021. Cases where drug suggestions were feasible underwent treatment with targeted molecular therapies and checkpoint inhibitor. We experienced cases where hereditary cancer syndromes such as Lynch syndrome were diagnosed through the detection of germline pathogenic variants.
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MSH6 (MutS homolog 6)
    |
    BRAF V600E • TMB-H • BRAF V600 • IDH1 R132H • TERT mutation • IDH wild-type • IDH1 R132 • IDH mutation + BRAF V600E
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
    1m
    Prospective germline sequencing of patients with gliomas, glioneuronal or neuronal tumors (SNO 2024)
    Clinical germline sequencing identifies a germline mutation in a high proportion of patients with CNS tumors. Biallelic inactivation was most commonly identified in tumors from patients with germline TP53 or NF1 mutations and were less common in patients with a germline MMR alteration.
    Clinical • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)
    |
    TP53 mutation • NF1 mutation • CHEK2 mutation • IDH wild-type
    |
    MSK-IMPACT
    1m
    CDKN2A homozygous deletion has stronger prognostic power than IDH mutation in CNS WHO grade 4 Gliomas. (SNO 2024)
    The presenting study suggest that CDKN2A deletion should play a powerful prognostic role in CNS WHO grade 4 gliomas as well as low grade glioma. Even if CNS WHO grade 4 gliomas had mutant IDH, they can have poor clinical outcome due to CDKN2A deletion.
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
    |
    CDKN2A deletion • CDKN2A mutation • IDH wild-type
    |
    OncoaccuPanel™
    1m
    Fusion transcriptome landscape in Glioblastoma (SNO 2024)
    Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
    |
    TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion
    |
    MI Tumor Seek™
    1m
    Flow cytometry identifies changes in peripheral and intrathecal lymphocyte patterns in CNS autoimmune disorders and primary CNS malignancies. (PubMed, J Neuroinflammation)
    ALE, RRMS, and pCNS-tumors show distinct but partially overlapping changes mainly in HLA-DR+ Tc, memory Tc, exhausted Tc, and Bc subsets providing insights into disease pathogenesis. Moreover, mFC shows diagnostic potential facilitating early diagnosis and treatment.
    Journal
    |
    CD20 (Membrane Spanning 4-Domains A1)
    |
    IDH wild-type
    1m
    Dynamic susceptibility contrast‑enhanced perfusion magnetic resonance imaging parameters for predicting MGMT promoter methylation and prognostic value in newly diagnosed patients with glioblastoma. (PubMed, Oncol Lett)
    The present study indicated that CBV and CBF could be used to predict the MGMT methylation status in glioblastomas. However, the prognostic value of tumor vascularity and MGMT methylation status may be limited.
    Journal • MRI
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    MGMT promoter methylation • IDH wild-type
    1m
    Single-cell transcriptomics reveals IRF7 regulation of the tumor microenvironment in isocitrate dehydrogenase wild-type glioma. (PubMed, MedComm (2020))
    This study systematically established the regulatory mechanism of IDH transcriptional activity in gliomas at the single-cell level and drew a corresponding cell map. The study presents a transcriptional regulatory activity map for IDH wild-type gliomas, involving single-cell RNA sequencing and spatial transcriptomics to identify gene regulatory networks, machine learning models for IDH subtyping, and experimental validation, highlighting the role of IRF7 in glioma progression.
    Journal
    |
    IRF7 (Interferon Regulatory Factor 7)
    |
    IDH wild-type
    1m
    Development and validation of a clinical risk model for postoperative outcome in newly diagnosed glioblastoma: a report of the RANO resect group. (PubMed, Neuro Oncol)
    The novel RANO risk model serves as an easy-to-use, yet highly prognostic tool for postoperative patient stratification prior to further therapy. The model may serve to guide patient management and reduce imbalances between study arms in prospective trials.
    Journal
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    1m
    Spermine Synthase : A Potential Prognostic Marker for Lower-Grade Gliomas. (PubMed, J Korean Neurosurg Soc)
    High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.
    Journal
    |
    CD8 (cluster of differentiation 8)
    |
    IDH wild-type
    2ms
    Extrachromosomal DNA driven oncogene spatial heterogeneity and evolution in glioblastoma. (PubMed, bioRxiv)
    Tumors with ecDNA amplified EGFR versus PDGFRA exhibit different evolutionary trajectories. SPECIES model can infer spatial evolutionary dynamics of ecDNA in cancer.A delay between ecDNA accumulation and subsequent oncogenic mutation may give a therapeutic window for early intervention.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    EGFR wild-type • IDH wild-type
    2ms
    Anatomy-guided resections for paralimbic tumors in the temporo-insular region: combining tumor and epilepsy surgery concepts. (PubMed, Front Neurol)
    The 2-year overall survival estimates were 96.0% for 24 primary diffuse CNS WHO grade 2 and 3 gliomas and 55.2% for 30 patients undergoing first surgeries for glioblastomas/astrocytomas CNS WHO grade 4. Combining both epilepsy and tumor surgery concepts in the surgical treatment of intrinsic brain tumors involving the mesial temporal lobe, often extending into the insula, led to more extensive resections, improved seizure outcomes, and potentially even better patient survival outcomes.
    Journal • Surgery
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH wild-type
    2ms
    Tumor Treating Fields (TTFields) Therapy and Lomustine Chemotherapy for the Treatment of Unresectable Progressive Glioblastoma. (PubMed, Case Rep Oncol)
    The patient experienced tumor pseudoprogression/progression after three cycles of maintenance temozolomide/TTFields therapy and again after a further two cycles of procarbazine/CCNU/TTFields therapy, and was then switched to CCNU/TTFields therapy. This patient case is reflective of the EF-14 study outcome using TTFields therapy beyond first progression concomitantly with chemotherapy. The observations from this case suggest that TTFields therapy concomitant with CCNU is a valuable treatment modality in patients with GBM, in this context.
    Journal
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    temozolomide • lomustine • Matulane (procarbazine hydrochloride)
    2ms
    NF1 expression profiling in IDH-wildtype glioblastoma: genomic associations and survival outcomes. (PubMed, Acta Neuropathol Commun)
    NF1 immunostaining may serve as a sensitive surrogate marker of NF1 genomic inactivation and a valuable extension to next-generation sequencing for defining NF1 status. Minimal NF1 immunoreactivity is a poor prognostic marker, even in IDH-wildtype glioblastoma without apparent NF1 genomic alterations, but the underlying molecular mechanism requires further investigation.
    Retrospective data • Journal
    |
    EGFR (Epidermal growth factor receptor) • NF1 (Neurofibromin 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
    |
    IDH wild-type
    2ms
    VIGAS2: A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients (clinicaltrials.gov)
    P2, N=220, Recruiting, Cecilia Soderberg-Naucler | Trial completion date: Aug 2024 --> Jul 2027 | Trial primary completion date: Aug 2024 --> Jul 2027
    Trial completion date • Trial primary completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    MGMT promoter methylation • IDH wild-type
    |
    temozolomide • Valcyte (valganciclovir)
    2ms
    Survival Determinants in Glioblastoma: An Insight into Biopsy-Only Patient Outcomes. (PubMed, Biomedicines)
    Age did not significantly affect survival outcomes (OR = 1.00, p = 0.835). Our findings reveal that any adjuvant treatment (whether chemotherapy and radiotherapy combined, chemotherapy alone, or bevacizumab), no contrast uptake on imaging, and higher pre-operative KPS are key determinants of survival in IDH-wildtype glioblastoma and should therefore be considered when deciding whether to perform a biopsy.
    Journal • Biopsy
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    Avastin (bevacizumab)
    2ms
    CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas. (PubMed, Biomedicines)
    The present study suggests that CDKN2A deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant IDH1/2, they may have poor clinical outcomes because of CDKN2A deletion.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH1 mutation • CDKN2A deletion • CDKN2A mutation • MGMT promoter methylation • IDH wild-type
    |
    OncoaccuPanel™
    2ms
    Dual phenotypes in recurrent astrocytoma, IDH-mutant; coexistence of IDH-mutant and IDH-wildtype components: a case report with genetic and epigenetic analysis. (PubMed, Acta Neuropathol Commun)
    Because these genetic abnormalities can drive oncogenic pathways, such as the PI3K/AKT/mTOR and RB signaling pathway, IDH-mutant gliomas that acquired these mutations were no longer dependent on the initial driver mutation, the IDH mutation. Molecular analysis of this unique case provides insight that in a subset of astrocytoma, IDH-mutant that acquired these genetic abnormalities, IDH mutation may not play a pivotal role in tumor growth and acquisition of these genetic abnormalities may contribute to the acquisition of resistance to IDH inhibitors.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    CDKN2A deletion • IDH wild-type
    2ms
    Macrophage polarization-related gene signature for risk stratification and prognosis of survival in gliomas. (PubMed, J Cell Mol Med)
    The differential expression of these genes between low-grade gliomas and glioblastomas was confirmed by q-RT-PCR. Macrophage polarization-related gene signatures can predict the malignancy and outcome of patients with gliomas and might act as a promising target for glioma immunotherapy in the future.
    Journal • Gene Signature • IO biomarker
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    2ms
    The Role of Systemic Therapies in the Treatment of Grades 1-4 Gliomas. (PubMed, Cureus)
    The beneficial impact of adding chemotherapy to radiotherapy (PCV: procarbazine, lomustine, vincristine) has also been demonstrated. In grade 4 glioblastoma multiforme (GBM), wild-type isocitrate dehydrogenase (IDH) status showed the best treatment outcomes with temozolomide (TMZ) in patients with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation...Bevacizumab (BEV) monotherapy can improve progression-free survival and maintain the initial quality of life. Despite advancements in GBM treatment, outcomes remain unsatisfactory, with a median survival of 14-16 months. Further research is still needed regarding the systemic treatment of central nervous system gliomas.
    Review • Journal
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    IDH wild-type
    |
    Avastin (bevacizumab) • temozolomide • vincristine • lomustine • Matulane (procarbazine hydrochloride)
    2ms
    A multi-center, clinical analysis of IDH-mutant gliomas, WHO Grade 4: implications for prognosis and clinical trial design. (PubMed, J Neurooncol)
    These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    CDKN2A deletion • CDKN2A mutation • IDH wild-type
    2ms
    PET/CT with 11C-methionine as a predictor of disease-free survival in patients with IDH1 wild type diffuse glioma (PubMed, Zh Vopr Neirokhir Im N N Burdenko)
    Diffuse IDH1wt gliomas are a heterogeneous group differing in metabolic characteristics and prognosis. PET/CT with 11C-methionine may be effective for stratifying patients into groups with unfavorable and favorable prognosis, as well as assessment of advisability of in-depth searching for IDH1/IDH2 mutation.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH wild-type
    2ms
    IDH2 Inhibitors Gain a Wildcard Status in the Cancer Therapeutics Competition. (PubMed, Cancers (Basel))
    Collectively, these reports highlight wild-type IDH2 as a promising therapeutic target, with potential applications as a two-edged sword in both cancer treatment and immunotherapy. The development of specific wild-type IDH2 inhibitors could offer new avenues for therapy, particularly in tumors reliant on IDH2 activity as well as in enhancing the effectiveness of CAR T cell therapies.
    Journal
    |
    CD8 (cluster of differentiation 8)
    |
    IDH wild-type
    2ms
    Looking Beyond the Surface: Olutasidenib and Ivosidenib for Treatment of mIDH1 Acute Myeloid Leukemia. (PubMed, Curr Treat Options Oncol)
    In biochemical studies, olutasidenib selectively inhibits mutant but not wild-type IDH1, whereas ivosidenib appears to potently block both mutant and wild-type IDH1. Although they have the same target, olutasidenib and ivosidenib have unique molecular features, which may translate to selectivity differences in their inhibitory activity against IDH1.
    Review • Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 mutation • IDH wild-type
    |
    Tibsovo (ivosidenib) • Rezlidhia (olutasidenib)
    2ms
    Combined Treatment of Camrelizumab and Bevacizumab for Adult Patients with Recurrent Glioblastoma (GBM) (clinicaltrials.gov)
    P2, N=3, Terminated, Beijing Sanbo Brain Hospital | N=94 --> 3 | Suspended --> Terminated; Lack of funds
    Enrollment change • Trial termination
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH wild-type
    |
    Avastin (bevacizumab) • AiRuiKa (camrelizumab)