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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
    3d
    NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)
    P2, N=51, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Dec 2027 --> Feb 2025 | Suspended --> Terminated; Abandon of the partner, GSK
    Trial completion date • Trial termination • Pan tumor • Platinum sensitive
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    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)
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    HER-2 positive • HER-2 amplification • DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
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    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    7d
    Integrated Genomic and Transcriptomic Profiling of Isolated Trisomies in AML Reveals Cell Cycle Dysregulation and Therapeutic Vulnerabilities. (PubMed, J Cell Mol Med)
    Drug sensitivity profiling revealed subgroup-specific vulnerabilities: IT-8 to DNA damage checkpoint inhibitors, IT-21 to PLK/mTOR inhibitors and IT-13+22 to BRAF/EGFR-targeted agents. These findings highlight AML-IT heterogeneity and therapeutic potential.
    Journal
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    BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CALR (Calreticulin) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • MCM4 (Minichromosome Maintenance Complex Component 4) • CDC25A (Cell Division Cycle 25A) • CDC7 (Cell Division Cycle 7) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1) • HSP90AB1 (Heat Shock Protein 90 Alpha Family Class B Member 1)
    8d
    A metabolic-radioimmune signature predicts therapy response and immune reprogramming in non-small cell lung cancer. (PubMed, Front Oncol)
    The RRMG signature predicts radioimmunotherapy outcomes for patient stratification. Identifying ouabain and novel compounds highlights targeting metabolic vulnerabilities as a translatable strategy to overcome resistance.
    Journal • IO biomarker
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    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ALDH3A1 (Aldehyde Dehydrogenase 3 Family Member A1)
    8d
    Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma. (PubMed, Genome Biol)
    This may reflect either relaxed positive selection for the mutant IDH1 locus, or negative selection for the hypermethylation phenotype later in tumor evolution. This finding highlights the challenge for therapeutic intervention by mutant IDH1 inhibitors in chondrosarcoma.
    Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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    IDH1 mutation • IDH2 mutation
    10d
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=695, Recruiting, AstraZeneca | Trial completion date: Apr 2027 --> Aug 2027 | Trial primary completion date: Apr 2027 --> Aug 2027
    Trial completion date • Trial primary completion date
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    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) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
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    HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation
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    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • AZD9574
    11d
    Mitochondrial bioenergetic signatures differentiate asymptomatic from symptomatic Alzheimer's disease. (PubMed, bioRxiv)
    In contrast, microglia and oligodendrocytes proportions were reduced in AsymAD relative to AD. Our findings identify preserved mitochondrial bioenergetics as a defining feature of resilience in AD and suggest that enhancing NADH metabolism via NAD+ precursor-based interventions may potentially help in maintaining cognitive function despite amyloid and tau pathology.
    Journal
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    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MB (Myoglobin) • MRPL47 (Mitochondrial Ribosomal Protein L47)
    11d
    Resistance to imatinib in a ETV6::PDGFRB rearranged myeloid/lymphoid neoplasm with high-risk mutations: a case report. (PubMed, Front Oncol)
    Platelet-derived growth factor receptor beta (PDGFRB)-rearranged myeloid/lymphoid neoplasms (MLNs) are rare hematologic malignancies typically responsive to tyrosine kinase inhibitors (TKIs) such as imatinib. The patient progressed to acute myeloid leukemia (AML) within 11 months despite sequential therapies including dasatinib and azacitidine-venetoclax, ultimately succumbing to sepsis. This case highlights the limitations of TKI monotherapy in MLNs with PDGFRB rearrangements and co-existing high-risk mutations, underscoring the importance of early molecular profiling and consideration of allogeneic hematopoietic stem cell transplantation in cases with poor risk features.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ASXL1 (ASXL Transcriptional Regulator 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1)
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    KRAS mutation • NRAS mutation • ASXL1 mutation • SRSF2 mutation
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    Venclexta (venetoclax) • dasatinib • imatinib • azacitidine
    16d
    SIRT3-IDH2 axis is a target of dietary fructose: implication of IDH2 as a key player in dietary carcinogen toxicity in mice colon. (PubMed, Exp Mol Med)
    Fructose promotes colon carcinogenesis by disrupting mitochondrial function and impairing DNA damage response mechanisms, particularly through SIRT3-IDH2 axis suppression. These findings highlight the critical role of mitochondrial dysfunction in fructose-induced carcinogenesis and suggest the SIRT3-IDH2 axis as a potential therapeutic target.
    Preclinical • Journal
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    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SIRT3 (Sirtuin 3)
    16d
    Tall cell carcinoma with reversed polarity of breast cancer: a rare case report and review of the literature. (PubMed, Front Oncol)
    The patient continues to be followed up for prognostic evaluation, and no recurrence or metastasis occurred until now. The case has represented a full view to gaining an improved understanding of TCCRP.
    Journal
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD163 (CD163 Molecule) • CD68 (CD68 Molecule)
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    PIK3CA mutation • IDH2 mutation • IDH2 R172
    18d
    Mesonephric-like metaplasia of the endometrium in a woman treated with letrozole: morphological, immunohistochemical and molecular analysis. (PubMed, Pathologica)
    These features appear consistent with a benign endometrial mesonephric-like metaplasia. Its relationships with hormone treatment and with MLA carcinogenesis remain to be defined.
    Journal
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NKX2-1 (NK2 Homeobox 1) • MME (Membrane Metalloendopeptidase) • GATA3 (GATA binding protein 3) • PAX8 (Paired box 8)
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    PIK3CA mutation • TP53 wild-type
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    letrozole
    22d
    Bevacizumab plus erlotinib in advanced solid cancers with Krebs cycle gene mutations: A multicenter phase II study (BRISK; KCSG AL22-16). (PubMed, Clin Cancer Res)
    Bevacizumab plus erlotinib demonstrated promising efficacy in tumors with Krebs cycle gene mutations, warranting further investigation beyond FH-deficient RCC.
    P2 data • Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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    Avastin (bevacizumab) • erlotinib
    22d
    Improved Detection of Minimal Residual Disease in AML: Validation of IDH1/2 ddPCR Assays in the Perspective of Treatment with Target Inhibitors. (PubMed, Int J Mol Sci)
    Comparison of IDH and NPM1 trends during follow-up revealed a statistically significant positive correlation, both in raw (β = 0.079, p = 0.001) and ranked data (β = 0.99, p = 0.004), suggesting a co-dynamic pattern potentially useful for surrogate monitoring. While our study cannot yet define the clinical role of IDH mutation assessment by ddPCR due to the lack of comparative follow-up studies, it establishes a solid methodological foundation for standardizing minimal residual disease evaluation via ddPCR, paving the way for future prospective validation.
    Journal • Tumor mutational burden • Minimal residual disease
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    TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1)
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    IDH1 mutation • NPM1 mutation • IDH1 R132 • IDH2 R172