Cancer
Malignant Central Nervous System Neoplasm
CI-CAN-00001115Explore in graph →
Loading cancer entity…
Cancer
CI-CAN-00001115Explore in graph →
Variants & evidence
259 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| IDH1 R1326 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 5 | accepted | EID480In patients with a glioblastoma, those with mutations at R132 of IDH1 had better overall survival than wild-type patients. PMID 19228619 · Yan et al., 2009 · Open in CIViC | civic |
| 〃 | Anaplastic AstrocytomaALIAS | Prognostic | B | Supports Better Outcome | 5 | accepted | EID481In patients with anaplastic astrocytoma, those with mutations at R132 of IDH1 had better overall survival than wild-type patients. PMID 19228619 · Yan et al., 2009 · Open in CIViC | civic |
| 〃 | Anaplastic AstrocytomaALIAS | Prognostic | B | Supports Better Outcome | 3 | accepted | EID348In patients with astrocytoma, the presence of IDH1 R132 mutation is prognostic for better survival compared to patients who harbor wild type mutation. PMID 19933982 · Dubbink et al., 2009 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 3 | accepted | EID349In patients with glioblastoma, those harboring IDH1 R132 mutation has higher overall survival compared to those who do not have IDH1 mutation. PMID 20127344 · Bleeker et al., 2010 · Open in CIViC | civic |
| Cetuximab | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID4032In a clinical study of 63 recurrent glioma patients, de novo glioblastoma patients treated with cetuximab monotherapy (n=27) and harboring IDH1 codon 132 mutation were associated with improved overal… (full text at CIViC) PMID 22199315 · Lv et al., 2011 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID3718In a clinical study of 63 recurrent glioma patients, de novo glioblastoma patients treated with cetuximab monotherapy (n=27) and harboring IDH1 codon 132 mutation were associated with improved overal… (full text at CIViC) PMID 22199315 · Lv et al., 2011 · Open in CIViC | civic |
| IDH1 R132H2 | ||||||||
| (diagnostic) | GlioblastomaCURATED_BROADER | Diagnostic | A | Supports Positive | 5 | submitted | EID8629In the 2016 WHO classification for CNS tumors, IDH-mutant glioblastoma is recognized as a distinct entity. Whereas IDH-wildtype glioblastoma constitutes about 90% of cases and correspond to de novo gl… (full text at CIViC) PMID 27157931 · Louis et al., 2016 · Open in CIViC | civic |
| Pan-Mutant-IDH1 Inhibitor Bay-1436032 | GlioblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID2325In an experimental study, glioblastoma cells expressing IDH1 R132H were associated with sensitivity to (bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide), comparable to cells expressing wi… (full text at CIViC) PMID 21045145 · Seltzer et al., 2010 · Open in CIViC | civic |
| IDH1 R132S1 | ||||||||
| Cetuximab | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | — | submitted | EID4033In a clinical study of 63 recurrent glioma patients, de novo glioblastoma patients treated with cetuximab monotherapy (n=27) and harboring IDH1 codon 132 mutation were associated with improved overal… (full text at CIViC) PMID 22199315 · Lv et al., 2011 · Open in CIViC | civic |
| IDH2 R1722 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 5 | accepted | EID482In patients with a glioblastoma, those with mutations at R172 of IDH2 had better overall survival than wild-type patients. PMID 19228619 · Yan et al., 2009 · Open in CIViC | civic |
| 〃 | Anaplastic AstrocytomaALIAS | Prognostic | B | Supports Better Outcome | 5 | accepted | EID483In patients with anaplastic astrocytoma, those with mutations at R172 of IDH2 had better overall survival than wild-type patients. PMID 19228619 · Yan et al., 2009 · Open in CIViC | civic |
| NTRK2 Fusion3 | ||||||||
| (oncogenic) | Brain GlioblastomaALIAS | Oncogenic | C | Supports Oncogenicity | 1 | accepted | EID10896From a retrospective review of 38,095 tumor samples from 33,997 patients that underwent fusion screening at Memorial Sloan Kettering Cancer Center, 87 tumors were found to be positive for an NTRK1, NT… (full text at CIViC) PMID 31375766 · Solomon et al., 2020 · Open in CIViC | civic |
| Larotrectinib | Anaplastic Ependymoma | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID10360An MRI in a previously healthy 6-year-old boy now presenting with neurologic abnormalities and seizures revealed a mass obstructing the foramen of Monro and diffuse leptomeningeal dissemination. The p… (full text at CIViC) PMID 34651095 · Mangum et al., 2021 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Predictive | ||||||
| KIT EXPRESSION1 | ||||||||
| Sunitinib | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID10180Phase II trial of sunitinib in 40 patients with first recurrence of primary glioblastoma. Median PFS 2.2 mo, median OS 9.2 mo, 5 stable disease >=6 months, no objective responses, so primary study end… (full text at CIViC) PMID 24311637 · Hutterer et al., 2014 · Open in CIViC | civic |
| LRP1B Deletion1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID1645A retrospective study of 178 glioblastoma patients found that LRP1B deletion (complete transcript, N=4 or focal transcript deletion of >150kb, N=13) was associated with a lower progress free survival … (full text at CIViC) PMID 26428308 · Tabouret et al., 2015 · Open in CIViC | civic |
| MDM2 Amplification1 | ||||||||
| Navtemadlin + RG7112Sequential | GlioblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 1 | submitted | EID9023Through the analysis of 10 patient-derived glioblastoma cells, AMG232 was found to have increased sensitivity in comparison to RG7112 with the average IC50 of 76nM vs. 720nM; thus indicating a 9.5 fol… (full text at CIViC) PMID 30022047 · Her et al., 2018 · Open in CIViC | civic |
| MET Amplification1 | ||||||||
| Crizotinib | GlioblastomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1565A 62 year old female was diagnosed with glioblastoma (GBM) WHO grade 4. Treatment included radiation, temozolomide and cediranib. MET amplification was found by FISH, and ALK and MET inhibitor crizoti… (full text at CIViC) PMID 22162573 · Chi et al., 2012 · Open in CIViC | civic |
| ST-EPN-ZFTA2 | ||||||||
| (prognostic) | Supratentorial Ependymoma ZFTA Fusion-Positive | Prognostic | B | Supports Better Outcome | 3 | accepted | EID11445An international multi-institutional study identified108 patients with a methylation profile of supratentorial ependymoma, ZFTA fusion-positive, by whole genome DNA methylation profiling. The study fo… (full text at CIViC) PMID 37287693 · Ng et al., 2023 · Open in CIViC | civic |
| 〃 | Supratentorial Ependymoma ZFTA Fusion-Positive | Prognostic | B | Supports Better Outcome | 3 | accepted | EID11447In a series of 54 cases of ependymoma diagnosed in children </= 3 years, methylation profiling of all tumours was undertaken as part of a prospective clinical trial (SJYC07 - maximal safe surgical res… (full text at CIViC) PMID 30976811 · Upadhyaya et al., 2019 · Open in CIViC | civic |
| MGMT Expression1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID7977In a trial of 68 glioblastoma patients treated with either temozolomide or semustine, MGMT expression was found to be inversely correlated with survival. Patients in the MGMT high expression group (n=… (full text at CIViC) PMID 24248532 · Wang et al., 2014 · Open in CIViC | civic |
| MGMT Promoter Methylation6 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 5 | accepted | EID491In patients with glioblastoma, those with methylated MGMT promoters have better overall survival than those with unmethylated promoters. PMID 15758010 · Hegi et al., 2005 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 4 | accepted | EID172MGMT promoter methylation was associated with increased overall and disease-free survival as well as tumor regression in patients with gliomas. PMID 11070098 · Esteller et al., 2000 · Open in CIViC | civic |
| Carmustine | GlioblastomaCURATED_BROADER | Predictive | B | Supports | ||||
| MGMT RS169062521 | ||||||||
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID822The T allele of the rs16906252 SNP was associated with MGMT methylation and low protein expression. Germline presence of the T allele increased the risk of glioblastoma development (adjusted odds rati… (full text at CIViC) PMID 25910840 · Rapkins et al., 2015 · Open in CIViC | civic |
| MGMT Underexpression2 | ||||||||
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID2899In this study, patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median… (full text at CIViC) PMID 17442989 · Chinot et al., 2007 · Open in CIViC | civic |
| 〃 | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID2903In 41 glioblastomas treated with temozolomide (TMZ) therapy (MGMT-immunopositive: n = 22, negative: n = 19), both progression free survival and overall survival were significantly better in MGMT-immun… (full text at CIViC) PMID 21331613 · Watanabe et al., 2011 · Open in CIViC | civic |
| MIR21 Overexpression1 | ||||||||
| (prognostic) | Anaplastic AstrocytomaALIAS | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID8001The expression of a set of miRNAs was evaluated by qRT-PCR in 124 astrocytoma (grade I-IV) samples and 60 adjacent normal tissue samples in order to determine miRNAs with altered expression in astrocy… (full text at CIViC) PMID 20219352 · Zhi et al., 2010 · Open in CIViC | civic |
| ZFTA Fusion1 | ||||||||
| (diagnostic) | Supratentorial Ependymoma ZFTA Fusion-Positive | Diagnostic | C | Supports Positive | 1 | accepted | EID11431In an analysis of 13 cases of supratentorial tumors with ZFTA rearrangements without RELA involvement, all were found to have DNA methylation profiles similar to ZFTA::RELA supratentorial ependymoma. … (full text at CIViC) PMID 34389065 · Tauziède-Espariat et al., 2021 · Open in CIViC | civic |
| MYC Amplification1 | ||||||||
| (prognostic) | MedulloblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 5 | submitted | EID7048Group 3 medulloblastomas with MYC amplifications are often associated with large cell/anaplastic histology, young patients, and overall poor prognosis. PMID 15328187 · Lamont et al., 2004 · Open in CIViC | civic |
| MYCN Amplification2 | ||||||||
| Arsenic Trioxide | MedulloblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID5327In a patient derived xenograft from a sonic hedgehog driven medulloblastoma patient, MYCN amplification conferred to resistance to SMO inhibition with Sonidegib. This PDX was shown to be responsive t… (full text at CIViC) PMID 23291299 · Kim et al., 2013 · Open in CIViC | civic |
| Sonidegib | MedulloblastomaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID5325In a sonic hedgehog driven medulloblastoma patient derived xenograft harbouring a MYCN amplification, SMO inhibitor Sonidegib did not have an effect on cell proliferation. PMID 24651015 · Kool et al., 2014 · Open in CIViC | civic |
| PA-NF1 + NF1 Mutation2 | ||||||||
| (diagnostic) | Anaplastic AstrocytomaALIAS | Diagnostic | B | Supports Positive | 4 | submitted | EID12268This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| Selumetinib | Anaplastic AstrocytomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID12270This study reported 47 neurofibromatosis type 1 (NF1) patients with biallelic inactivation of NF1 genes were detected in all glial tumors. Targeted capture-based next-generation sequencing (479 cancer… (full text at CIViC) PMID 35945463 · Lucas et al., 2022 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| (oncogenic) | GlioblastomaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 4 | submitted | EID10930RNAseq data of 162 glioblastoma patients identified NTRK1 fusions with both NFASC and BCABN. By analyzing exome and RNA data, the NFASC-NTRK1 fusion was found to retain NTRK1's kinase and transmembran… (full text at CIViC) PMID 24647444 · Kim et al., 2014 · Open in CIViC | civic |
| NTRK3 EXPRESSION1 | ||||||||
| (prognostic) | MedulloblastomaCURATED_BROADER | Prognostic | B | Supports Positive | 3 | submitted | EID1968Patients with tumors expressing high levels of trkC mRNA had significantly longer intervals without disease progression than those with low levels (log-rank, P = 0.03) and a more favorable overall sur… (full text at CIViC) PMID 7809137 · Segal et al., 1994 · Open in CIViC | civic |
| NTRK3 Fusion1 | ||||||||
| Entrectinib | Desmoplastic/Nodular Medulloblastoma | Predictive | C | Does Not Support Sensitivity Response | 2 | submitted | EID12608In the STARTRK-NG Phase 1/2 trial of entrectinib in pediatric patients, with extracranial solid tumors or primary CNS tumors, aged <22 years with relapsed or refractory disease, tumors with fusions… (full text at CIViC) PMID 35395680 · Desai et al., 2022 · Open in CIViC | civic |
| PIK3CA Mutation1 | ||||||||
| Buparlisib | GlioblastomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID7072In this multicenter, open-label, multi-arm, phase 2 trial, 65 patients with PI3K pathway aberrations (defined by PTEN and pAKT IHC-Status in 95%, genomic testing in 5%) were treated with the PI3K inhi… (full text at CIViC) PMID 30715997 · Wen et al., 2019 · Open in CIViC | civic |
| PIK3R1 Mutation1 | ||||||||
| Buparlisib | GlioblastomaCURATED_BROADER | Predictive | B | Does Not Support Sensitivity Response | 3 | submitted | EID7073In this multicenter, open-label, multi-arm, phase 2 trial, 65 patients with PI3K pathway aberrations (defined by PTEN and pAKT IHC-Status in 95%, genomic testing in 5%) were treated with the PI3K inhi… (full text at CIViC) PMID 30715997 · Wen et al., 2019 · Open in CIViC | civic |
| PLK1 OVEREXPRESSION1 | ||||||||
| (prognostic) | GlioblastomaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 2 | submitted | EID8005Kaplan-Meier analysis of PLK1 gene expression showed that elevated expression is significantly associated with shorter disease-free survival in GBM (p=9.1e-11). PMID 32180229 · Li et al., 2020 · Open in CIViC | civic |
| PMS2 K706FS*191 | ||||||||
| Nivolumab | GlioblastomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 4 | accepted | EID1214Two siblings (6 and 3.5 years) from nonconsanguineous parents were diagnosed with glioblastoma multiforme. Both tumors harbored TP53 mutations and lack of MGMT promoter hypermethylation as poor progno… (full text at CIViC) PMID 27001570 · Bouffet et al., 2016 · Open in CIViC | civic |
| POLE Mutation1 | ||||||||
| Pembrolizumab | GlioblastomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1861Case report of a patient with glioblastoma multiforme and POLE germline mutation. The patient was treated with pembrolizumab and lymphocyte infiltration was noted after resection of a spinal metastasi… (full text at CIViC) PMID 27683556 · Johanns et al., 2016 · Open in CIViC | civic |
| PTCH1 Deletion1 | ||||||||
| Sonidegib | MedulloblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID5326In a sonic hedghehog driven medulloblastoma patient derived xenograft harbouring a PTCH1 deletion, SMO inhibition with Sonidegib showed inhibition of proliferation. PMID 24651015 · Kool et al., 2014 · Open in CIViC | civic |
| PTCH1 LOH1 | ||||||||
| Vismodegib | MedulloblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 2 | accepted | EID749Loss-of-heterozygosity in SHH-driven medulloblastoma was associated with increased PFS under therapy with vismodegib (AKA HhAntag691, GDC0449, GDC-0449). 43 patients total were enrolled for this study… (full text at CIViC) PMID 26169613 · Robinson et al., 2015 · Open in CIViC | civic |
| PTCH1 Mutation1 | ||||||||
| Sonidegib | MedulloblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID748133 sonic-hedghog driven medulloblastomas were sequenced for alterations (WGS or WES). 60 cases exhibited PTCH1 mutations, most of which were likely loss-of-function (spread across the gene and of typ… (full text at CIViC) PMID 24651015 · Kool et al., 2014 · Open in CIViC | civic |
| PTEN Expression2 | ||||||||
| Dacomitinib | GlioblastomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | accepted | EID775In this preclinical study, the EGFR inhibitor dacomitinib had an effect on cell viability, self-renewal and proliferation in EGFR amplified GBM cells in-vitro and in-vivo (with or without the EGFRvIII… (full text at CIViC) PMID 25939761 · Zahonero et al., 2015 · Open in CIViC | civic |
| Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor | GlioblastomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID77449 patients (26 pretreatment tissues available for analysis) with recurrent glioblastomas who were treated with EGFR TKIs were analyzed in this study. Results were confirmed in an independent cohort o… (full text at CIViC) PMID 16282176 · Mellinghoff et al., 2005 · Open in CIViC | civic |
Data updated 15 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Supports Sensitivity Response |
| 3 |
| accepted |
EID10361An MRI of 26-year-old man presenting with motor weakness and language difficultly revealed a lesion in the left frontal lobe that extended across the corpus callosum. Histologic analysis of the biopsy… (full text at CIViC) PMID 34041811 · Shepherd et al., 2021 · Open in CIViC |
| civic |
| 4 |
| accepted |
EID308MGMT promoter methylation has been shown to confer sensitivity to alkylating agents, such as carmustine, in glioblastoma cells. PMID 11070098 · Esteller et al., 2000 · Open in CIViC |
| civic |
| Lomustine + TemozolomideCombination | GlioblastomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | submitted | EID7303In a small Phase 3 trial, patients with newly diagnosed glioblastoma with methylation of the MGMT promoter randomely assigned to lomustine plus temozolomide in addition to radiotherapy (n=66) or temoz… (full text at CIViC) PMID 30782343 · Herrlinger et al., 2019 · Open in CIViC | civic |
| O6-Benzylguanine | GlioblastomaCURATED_BROADER | Predictive | E | Supports Sensitivity Response | 4 | accepted | EID309In patients lacking MGMT promoter methylation, the use of an MGMT inhibitor, such as O(6)-benzylguanine, in combination with alkylating agents (Carmustine) may be useful in treating patients with init… (full text at CIViC) PMID 11070098 · Esteller et al., 2000 · Open in CIViC | civic |
| Temozolomide | GlioblastomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID307In a randomized clinical trial, patients with MGMT promoter methylation benefitted from temozolomide. This benefit was also methylation status dependent, as those without methylation did not see incre… (full text at CIViC) PMID 15758010 · Hegi et al., 2005 · Open in CIViC | civic |