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    GENE:

    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

    i
    Other names: 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
    4d
    T cells and pembrolizumab for recurrent and newly diagnosed glioblastoma (ACTRN12623001126606)
    P1/2, N=58, Recruiting, QIMR Berghofer Medical Research Institute | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Virus specific T cells
    |
    EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler)
    |
    EGFR amplification
    |
    Keytruda (pembrolizumab)
    5d
    Emerging DNA Methylome Targets in FLT3-ITD-Positive Acute Myeloid Leukemia: Combination Therapy with Clinically Approved FLT3 Inhibitors. (PubMed, Curr Treat Options Oncol)
    Hence, FLT3 is considered an attractive druggable target; selective small FLT3 inhibitors (FLT3Is), such as midostaurin and quizartinib, have been clinically approved. Therefore, understanding the role of different epigenetic alterations in FLT3-ITD AML pathogenesis and how they modulate FLT3I's activity is important to rationalize combinational treatment approaches including FLT3Is and modulators of methylation regulators or pathways. Data from ongoing pre-clinical and clinical studies will further precisely define the potential use of epigenetic therapy together with FLT3Is especially after characterized patients' mutational status in terms of FLT3 and DNA methlome regulators.
    Review • Journal • Combination therapy
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
    |
    FLT3-ITD mutation
    |
    Rydapt (midostaurin) • Vanflyta (quizartinib)
    7d
    Extent of Resection Thresholds in Molecular Subgroups of Newly Diagnosed Isocitrate Dehydrogenase-Wildtype Glioblastoma. (PubMed, Neurosurgery)
    Our results suggest that a subset of molecularly defined GBM IDH-wildtype may benefit more from aggressive resections. Re-resections to optimize EOR might be beneficial in a subset of molecularly defined GBMs. Molecular alterations should be taken into consideration for surgical treatment decisions in GBM IDH-wildtype.
    Journal
    |
    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH wild-type
    7d
    IDHENTIFY: An Efficacy and Safety Study of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation (clinicaltrials.gov)
    P3, N=319, Completed, Celgene | Active, not recruiting --> Completed
    Trial completion
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    IDH2 mutation • UGT1A1*1*1 • UGT1A1 mutation
    |
    Abbott RealTime IDH2
    |
    cytarabine • azacitidine • Idhifa (enasidenib) • hydroxyurea
    8d
    Association of Clinical, Tumor, and Treatment Characteristics With Seizure Control in Patients With IDH1/2-Mutant Lower-Grade Glioma. (PubMed, Neurology)
    This study analyzed seizure control in patients with IDH1/2-mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH-mutant lower-grade glioma.
    Retrospective data • 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
    10d
    Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma. (PubMed, Cancers (Basel))
    Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)
    |
    TP53 mutation • KRAS mutation • BRAF mutation • ARID1A mutation • FGFR2 mutation • FGFR2 fusion • BAP1 mutation
    11d
    A comparative analysis of the clinical and genetic profiles of blast phase BCR::ABL1-negative myeloproliferative neoplasm and acute myeloid leukemia, myelodysplasia-related. (PubMed, Int J Lab Hematol)
    MPN-BP and AML-MR harbor similar somatic mutations and clinical outcomes, suggesting a unified clinical disease entity.
    Journal
    |
    TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1) • CALR (Calreticulin)
    |
    TP53 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • U2AF1 mutation
    12d
    T cells take aim in AML: targeting IDH2. (PubMed, Blood)
    No abstract available
    Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    12d
    RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives. (PubMed, Blood Cancer J)
    Recent evidence also indicates that RAS mutations drive resistance to targeted therapies, particularly FLT3, IDH1/2, or JAK2 inhibitors, as well as the venetoclax-azacitidine combination. The success of direct RAS inhibitors in patients with solid tumors has brought renewed optimism that this progress will be translated to patients with hematologic malignancies. In this review, we highlight key insights on RAS mutations across myeloid malignancies from the past decade, including their prevalence and distribution, cooperative genetic events, clonal architecture and dynamics, prognostic implications, and therapeutic targeting.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • RAS (Rat Sarcoma Virus)
    |
    RAS mutation
    |
    Venclexta (venetoclax) • azacitidine
    12d
    Wild-type IDH2 is a therapeutic target for triple-negative breast cancer. (PubMed, Nat Commun)
    Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.
    Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HIF1A (Hypoxia inducible factor 1, alpha subunit)
    |
    IDH wild-type
    |
    doxorubicin hydrochloride
    12d
    A validated LC-MS/MS method for determination of neuro-pharmacokinetic behavior of niraparib in brain tumor patients. (PubMed, J Pharm Biomed Anal)
    The validated method is currently employed to assess niraparib levels in human glioblastoma tissue, CSF, and plasma in an ongoing trial on newly diagnosed glioblastoma and recurrent IDH1/2(+) ATRX mutant glioma patients (NCT05076513). Initial results of calculated total (Kp) and unbound (Kp,uu) tumor-to-plasma partition coefficients indicate significant brain penetration ability of niraparib in glioblastoma patients.
    PK/PD data • Journal • PARP Biomarker
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler)
    |
    ATRX mutation
    |
    Zejula (niraparib)
    13d
    Genomic landscape of glioblastoma without IDH somatic mutation in 42 cases: a comprehensive analysis using RNA sequencing data. (PubMed, J Neurooncol)
    RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • SOX10 (SRY-Box 10)
    |
    TP53 mutation • EGFR mutation • FGFR3 fusion
    13d
    Clinical and imaging characteristics of supratentorial slioma with IDH2 mutation. (PubMed, Neuroradiology)
    A high frequency of oligodendrogliomas with 1p/19q codeletion was observed in IDH2-mutated gliomas. Younger age and the presence of the T2-FLAIR discordance were associated with IDH2 mutations and these findings may help with precise diagnoses and treatment decisions in clinical practice.
    Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH wild-type
    18d
    IDEAL Study: IDH2 (AG 221) Inhibitor in Patients With IDH2 Mutated Myelodysplastic Syndrome (clinicaltrials.gov)
    P2, N=68, Active, not recruiting, Groupe Francophone des Myelodysplasies | Recruiting --> Active, not recruiting | Trial completion date: Feb 2023 --> Mar 2026
    Enrollment closed • Trial completion date
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation
    |
    Idhifa (enasidenib)
    21d
    Pediatric-type high-grade gliomas with PDGFRA amplification in adult patients with Li-Fraumeni syndrome: clinical and molecular characterization of three cases. (PubMed, Acta Neuropathol Commun)
    These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TERT (Telomerase Reverse Transcriptase)
    |
    TP53 mutation • EGFR mutation • EGFR amplification • TERT mutation • IDH wild-type • TERT promoter mutation • PDGFR wild-type
    23d
    Data-driven modeling of core gene regulatory network underlying leukemogenesis in IDH mutant AML. (PubMed, NPJ Syst Biol Appl)
    The constructed core regulatory network and outcomes of in-silico network perturbations are supported by survival data from AML patients. We expect that the combined bioinformatics and systems-biology modeling approach will be generally applicable to elucidate the gene regulation of disease progression.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT1 (DNA methyltransferase 1) • E2F1 (E2F transcription factor 1)
    |
    IDH1 mutation • IDH2 mutation
    23d
    Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review. (PubMed, Exp Hematol Oncol)
    Targeted treatments have demonstrated preclinical efficacy over chemotherapy as an alternative or adjuvant to the current standard of care for GBM, but their clinical efficacy remains hindered by challenges such as blood-brain barrier penetrance of the drugs. The development of combinatorial targeted therapies is expected to improve therapeutic efficacy and overcome drug resistance.
    Review • Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    26d
    Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia. (PubMed, Leukemia)
    The emergence of these novel agents in AML offers patients a new modality of therapy, and shifts treatment paradigms toward individualized medicine. In this review, we outline the role of IDH mutations in malignant transformation, focus in on a novel group of targeted therapeutic agents directed toward IDH1- and IDH2-mutant AML, and explore their impact on prognosis in patients with AML.
    Review • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • FLT3 mutation
    29d
    Innovations in conditioning and post-transplant maintenance in AML: genomically informed revelations on the graft-versus-leukemia effect. (PubMed, Front Immunol)
    There is an urgent need to better understand how these emerging therapies modulate the two sides of the GVHD vs. GVL coin: 1) how molecularly or immunologically targeted therapies affect engraftment, GVHD potential, and function of the donor graft and 2) how these therapies affect the immunogenicity and sensitivity of leukemic clones to the GVL effect. By maximizing the synergistic action of molecularly targeted agents, immunomodulating agents, conventional chemotherapy, and the GVL effect, there is hope for improving outcomes for patients with this often-devastating disease.
    Review • Journal • Post-transplantation
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    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    1m
    Ascorbic Acid and Chemotherapy for the Treatment of Relapsed or Refractory Lymphoma, CCUS, and Chronic Myelomonocytic Leukemia (clinicaltrials.gov)
    P2, N=80, Recruiting, Mayo Clinic | N=55 --> 80
    Enrollment change
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CD4 (CD4 Molecule) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    IDH2 mutation • DNMT3A mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation
    |
    cisplatin • carboplatin • gemcitabine • Rituxan (rituximab) • cytarabine • cyclophosphamide • ifosfamide • oxaliplatin • etoposide IV • decitabine • Hemady (dexamethasone tablets) • Mabtas (rituximab biosimilar) • Starasid (cytarabine ocfosfate) • dexamethasone injection
    1m
    Somatic gene mutation patterns and burden influence outcomes with enasidenib in relapsed/refractory IDH2-mutated AML. (PubMed, Leuk Res)
    In multivariable analyses, RAS and RTK pathway mutations were significantly associated with decreased overall survival, after adjusting for treatment arm, IDH2 variant, and mutational burden. Importantly, enasidenib-mediated survival benefit was more pronounced in patients with IDH2-R172 variants.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1)
    |
    NRAS mutation • IDH2 mutation • DNMT3A mutation • TMB-L • IDH2 R140 • IDH2 R172
    |
    Idhifa (enasidenib)
    1m
    Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. (PubMed, J Clin Pharmacol)
    This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 probe drug), midazolam (CYP3A4 probe drug), omeprazole (CYP2C19 probe drug), and pioglitazone (CYP2C8 probe drug), in patients with AML or myelodysplastic syndrome. The parameters for omeprazole increased by 1.86 (90% CI: 1.33, 2.60) and 1.47 (0.93, 2.31)-fold, respectively, compared to omeprazole alone, while those for pioglitazone decreased to 0.80 (90% CI: 0.62, 1.03) and 0.87 (90% CI: 0.65, 1.16)-fold, respectively, in comparison to pioglitazone alone. These findings provide valuable insights into dose recommendations concerning drugs acting as substrates of CYP2D6, CYP2C9, CYP3A4, CYP2C19, and CYP2C8 when administered concurrently with enasidenib.
    Journal
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    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CYP2C9 (Cytochrome P450 Family 2 Subfamily C Member 9) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    IDH2 mutation
    |
    Idhifa (enasidenib)
    1m
    Comprehensive Immunogenomic Profiling of IDH1-/2-Altered Cholangiocarcinoma. (PubMed, JCO Precis Oncol)
    Significant differences in GA and immune biomarkers are noted between IDH1/2+ and IDHwt iCCA. IDH1-/2-mutated tumors appear immunologically cold without gLOH. These immunogenomic data provide insight for precision targeting of iCCA with IDH alterations.
    Journal • Retrospective data • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • PD-1 (Programmed cell death 1) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1) • CD70 (CD70 Molecule)
    |
    PD-L1 expression • MSI-H/dMMR • IDH1 mutation • HRD • VTCN1 underexpression • IDH1 R132C • IDH wild-type • IDH1 R132 • VTCN1 expression • IDH1 R132L • IDH2 R140 • IDH2 R172
    |
    PD-L1 IHC 22C3 pharmDx
    1m
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=490, Recruiting, AstraZeneca | Trial primary completion date: Apr 2025 --> Jan 2026
    Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • datopotamab deruxtecan (DS-1062a) • AZD9574
    1m
    Blastic plasmacytoid dendritic cell tumor treated with DVT regimen: a case report and literature review (PubMed, Zhonghua Xue Ye Xue Za Zhi)
    The patient with skin nodules and the pathology diagnosed BPDCN, the next generation sequencing of skin nodules showed mutations of IDH2 and ASXL1. DVT (decitabine combined with Venetoclax and thalidomide) has significant efficacy with rapid and deep remission for BPDCN, and the adverse effects is less, especially suitable for elderly patients who cannot tolerate intense chemotherapy.
    Review • Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ASXL1 (ASXL Transcriptional Regulator 1)
    |
    IDH2 mutation • ASXL1 mutation
    |
    Venclexta (venetoclax) • decitabine • thalidomide
    1m
    ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas (clinicaltrials.gov)
    P1, N=18, Recruiting, Massachusetts General Hospital | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2022 --> May 2024
    Trial completion date • Trial primary completion date
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation
    |
    Inqovi (decitabine/cedazuridine)
    1m
    Triple-Negative Myelofibrosis: Disease Features, Response to Treatment and Outcomes. (PubMed, Clin Lymphoma Myeloma Leuk)
    TN-MF is invariably associated with significantly decreased survival and more aggressive clinical behavior with higher rates of leukemic transformation and shorter duration of response to ruxolitinib. Mutations impacting RNA splicing, epigenetic modification and signaling (SRSF2, SETBP1, IDH2, CBL, and GNAS) are more common in TN-MF, which likely drive its aggressive course and may account for suboptimal responses to JAK inhibition.
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1) • GNAS (GNAS Complex Locus) • CALR (Calreticulin)
    |
    ASXL1 mutation • SRSF2 mutation • LDH-L
    |
    Jakafi (ruxolitinib)
    1m
    A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma. (PubMed, EBioMedicine)
    Overall, this work provides preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas.
    Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation
    |
    Idhifa (enasidenib)
    1m
    Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies. (PubMed, J Pers Med)
    The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.
    Review • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • COL2A1 (Collagen Type II Alpha 1 Chain)
    |
    MG132
    1m
    Electrochemical Nanoreactor Provides a Comprehensive View of Isocitrate Dehydrogenase Cancer-drug Kinetics. (PubMed, Angew Chem Weinheim Bergstr Ger)
    Ivosidenib, used to treat acute myeloid leukemia, acts on a common cancer-linked variant of isocitrate dehydrogenase 1 (IDH1 R132H) inhibiting its "gain-of-function" activity-the undesired reduction of 2-oxoglutarate (2OG) to the oncometabolite 2-hydroxyglutarate (2HG)...Such details, essential for understanding inhibition mechanisms, are not readily resolved in conventional steady-state kinetics or by techniques that rely only on measuring binding. Extending the new method and analytical framework presented here to other enzyme systems will be straightforward and should rapidly reveal insight that is difficult or often impossible to obtain using other methods.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH1 R132H • IDH1 R132
    |
    Tibsovo (ivosidenib)
    1m
    NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)
    P2, N=51, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=112 --> 51 | Trial completion date: Mar 2027 --> Dec 2027 | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024
    Enrollment change • Trial completion date • Trial suspension • Trial primary completion date • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
    |
    HER-2 positive • HER-2 amplification • DDR • PBRM1 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD
    |
    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    1m
    If it's a target, it's a pan-cancer target: Tissue is not the issue. (PubMed, Cancer Treat Rev)
    Hence, we now have multiple genomic biomarker-based, tissue-agnostic Food and Drug Administration approvals for both gene- and immune-targeted therapies (larotrectinib/entrectinib, for NTRK fusions; selpercatinib, RET fusions; dabrafenib plus trametinib, BRAFV600E mutations; pembrolizumab/dostarlimab, microsatellite instability; and pembrolizumab for high tumor mutational burden; pemigatinib is also approved for FGFR1-rearranged myeloid/lymphoid neoplasms). Resistance to biomarker-driven therapeutics is often due to secondary mutations or co-driver gene defects; studies are now addressing the need for customized drug combinations matched to the complex molecular alteration portfolio in each tumor. Future investigation should expand tissue-agnostic therapeutics to encompass both hematologic and solid malignancies and include biomarkers beyond those that are DNA-based.
    Review • Journal • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • NRG1 (Neuregulin 1) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • TMB-H • KRAS G12C • BRAF V600 • RET fusion • KRAS G12 • NTRK fusion
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Retevmo (selpercatinib) • Jemperli (dostarlimab-gxly) • Pemazyre (pemigatinib)
    2ms
    Study of Orally Administered AG-881 in Patients With Advanced Solid Tumors, Including Gliomas, With an IDH1 and/or IDH2 Mutation (clinicaltrials.gov)
    P1, N=95, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: Dec 2023 --> Mar 2024
    Trial completion date • Metastases
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH1 mutation • IDH2 mutation
    |
    vorasidenib (S95032)
    2ms
    An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 When Administered Alone and in Combination With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML) (clinicaltrials.gov)
    P1/2, N=70, Terminated, Kartos Therapeutics, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jul 2024 --> Sep 2023 | Active, not recruiting --> Terminated; In September 2023, the study was terminated because of a Sponsor decision, unrelated to safety concerns.
    Phase classification • Trial completion date • Trial termination • Combination therapy
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    cytarabine • decitabine • navtemadlin (KRT-232) • Depocyte (liposomal cytarabine)
    2ms
    Genetic alterations in myeloid sarcoma among acute myeloid leukemia patients: insights from 37 cohort studies and a meta-analysis. (PubMed, Front Oncol)
    This meta-analysis sheds light on the prevalence of genetic mutations in AML patients with MS, providing insights into the unique characteristics of the mutations and their frequencies. These discoveries are crucial in informing therapeutic and prognostic decisions for individuals with myeloid sarcoma.
    Retrospective data • Review
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    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    NRAS mutation • FLT3-ITD mutation • IDH2 mutation • CEBPA mutation
    2ms
    Ascorbic Acid and Combination Chemotherapy for the Treatment of Relapsed or Refractory Lymphoma or CCUS (clinicaltrials.gov)
    P2, N=55, Recruiting, Mayo Clinic | Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CD4 (CD4 Molecule) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
    |
    IDH2 mutation • DNMT3A mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation
    |
    cisplatin • carboplatin • gemcitabine • Rituxan (rituximab) • cytarabine • cyclophosphamide • ifosfamide • oxaliplatin • etoposide IV • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate) • dexamethasone injection
    2ms
    Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities. (PubMed, Virchows Arch)
    As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • AFF2 (AF4/FMR2 family member 2) • NUTM1 (NUT Midline Carcinoma Family Member 1)
    2ms
    Genetically Distinct Oligosarcoma Arising from Oligodendroglioma: Systematic Review & Illustrative Case Example. (PubMed, World Neurosurg)
    Oligosarcoma is a prognostically unfavorable CNS neoplasm with characteristic imaging and pathologic features, and a strong association with previously resected oligodendroglioma. Aggressive treatment is recommended, including gross total resection and adjuvant chemoradiation. Further study is required to define optimal treatment protocol for this CNS malignancy.
    Review • Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • YAP1 (Yes associated protein 1)
    |
    IDH2 mutation • CDKN2A deletion
    2ms
    Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov)
    P1/2, N=150, Recruiting, Nerviano Medical Sciences | N=75 --> 150
    Enrollment change
    |
    EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase)
    |
    EGFR mutation • EGFR amplification • MGMT promoter methylation • TERT mutation • IDH wild-type • TERT promoter mutation
    |
    temozolomide • NMS-293
    2ms
    SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)
    P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)
    |
    HER-2 mutation • BAP1 mutation • AKT1 mutation • FGFR3 fusion • JAK3 mutation
    2ms
    Integrating Full Bayesian Inference and Student's t-Distribution Method for Enhanced Outlier Handling in Caffeine Population Pharmacokinetics: Assessing Drug-Drug Interactions with Enasidenib in Relapsed or Refractory AML and MDS Patients. (PubMed, J Clin Pharmacol)
    This finding led to a specific recommendation in the package insert to avoid the concurrent use of certain CYP1A2 substrates with enasidenib, unless directed otherwise in the prescribing information. Furthermore, this research underlines the technical benefits of integrating full Bayesian inference and incorporating Student's t-distribution for residual error modeling in the PK field.
    PK/PD data • Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CYP1A2 (Cytochrome P450, family 1, subfamily A, polypeptide 2)
    |
    IDH2 mutation
    |
    Idhifa (enasidenib)
    2ms
    The Impact of Mutational Hotspots on Cancer Survival. (PubMed, Cancers (Basel))
    Our analysis revealed both known and putatively novel hotspots associated with survival, which can be used as biomarkers. Our web resource is a valuable tool for cancer research.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    TP53 mutation • EGFR mutation • PIK3CA mutation