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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
    16h
    If it is a solid tumor target, then it may be a hematologic cancer target: Bridging the great divide. (PubMed, Med)
    They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAFV600E mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms...For example, BRAFV600E and IDH1/2 mutations; ALK, FGFR, and NTRK fusions; PD-L1 amplification; and CD70 antigens are druggable in both solid and blood malignancies by gene-/immune-targeted therapies/chimeric antigen receptor T cells. Future biomarker-based tissue-agnostic basket studies/approvals should bridge the great divide and include both solid and hematologic cancers.
    Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • 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) • CD70 (CD70 Molecule) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • TMB-H • BRAF V600 • HER-2 expression • RET fusion • FGFR mutation • FGFR fusion • PD-L1 amplification • FGFR1 expression • IDH mutation + BRAF V600E • IDH mutation + NTRK fusion • NTRK fusion
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Retevmo (selpercatinib) • Jemperli (dostarlimab-gxly) • Pemazyre (pemigatinib) • Augtyro (repotrectinib)
    1d
    Genomic Profiling in Glioma Patients to Explore Clinically Relevant Markers. (PubMed, Int J Mol Sci)
    In IDH-wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS...Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler)
    |
    TP53 mutation • PIK3CA mutation • IDH1 mutation • PTEN deletion • PTEN mutation • TERT mutation • IDH mutation + Chr del(1p) + Chr del(19q)
    |
    Avastin (bevacizumab)
    1d
    Non-Susceptibility Gene Variants in Head and Neck Paragangliomas. (PubMed, Int J Mol Sci)
    A functional network analysis of the mutated genes revealed numerous associations and a list of metabolic pathways (e.g., the TCA cycle, carbon metabolism, pyruvate metabolism, etc.) and signaling pathways (e.g., HIF1, PI3K-Akt, FoxO, AMPK, MAPK, etc.) that may play an important role in the development of HNPGLs. The identified range of genetic alterations affecting multiple genes and, potentially, influencing diverse cellular pathways provides an enhanced molecular genetic characterization of HNPGLs.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1)
    1d
    Biological Markers of Myeloproliferative Neoplasms in Children, Adolescents and Young Adults. (PubMed, Cancers (Basel))
    Although rare, myeloproliferative neoplasms can involve young patients and pose unique challenges for clinicians in diagnosis and therapy. The paper aims to review the biological markers of MPNs in pediatric populations-a particular group of patients that has been poorly studied due to the low frequency of MPN diagnosis.
    Review • Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CALR (Calreticulin)
    7d
    Sustained yet non-curative response to lenalidomide in relapsed angioimmunoblastic T-cell lymphoma with acquired chidamide resistance: a case report with 10-year follow-up, genetic insights and literature review. (PubMed, Front Oncol)
    Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.
    Review • Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • RHOA (Ras homolog family member A)
    |
    ARID1A mutation • TET2 mutation • KMT2D mutation • Chr del(5q)
    |
    lenalidomide • Epidaza (chidamide)
    9d
    Acute myeloid leukemia treatment outcomes with isocitrate dehydrogenase mutations: A systematic review and meta-analysis. (PubMed, Medicine (Baltimore))
    Different subtypes of IDH mutations may lead to different AML prognoses, suggesting the feasibility of personalized treatment for AML patients.
    Clinical • Retrospective data • Review • Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH1 mutation • IDH2 mutation
    9d
    Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)
    P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date • Metastases
    |
    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) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation
    |
    Talzenna (talazoparib)
    9d
    The expression of DNAJB9 in normal human astrocytes is more sensitive to nanographene oxide than in glioblastoma cells. (PubMed, Endocr Regul)
    Conclusion. The data obtained demonstrate that the low doses of nGO disturbed the functional integrity of the genome preferentially through ER stress signaling and exhibit a more pronounced genotoxic effect in the normal astrocytes than the glioblastoma cells.
    Journal
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    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATF4 (Activating Transcription Factor 4) • DDIT3 (DNA-damage-inducible transcript 3) • ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1) • ATF3 (Activating Transcription Factor 3)
    11d
    Molecular testing of gastrointestinal tumours - current status and future prospects. (PubMed, Rozhl Chir)
    In gallbladder and biliary tract cancers, we are mainly looking for IDH1 and IDH2 mutations, FGFR2 gene fusions and mutations, HER2 amplifications or mutations, as well as mutations of BRAF or BRCA1/2. All results should be discussed within the molecular tumor board.
    Review • Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    PD-L1 expression • BRCA2 mutation • BRCA1 mutation • BRAF mutation • HER-2 amplification • NRAS mutation • HER-2 expression • IDH2 mutation • FGFR2 mutation • FGFR2 fusion • HER-2 amplification + PD-L1 expression
    11d
    Mutation- and MRD-informed treatments for transplant-ineligible patients. (PubMed, Hematology Am Soc Hematol Educ Program)
    The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups...Additional studies defining the prognostic role of measurable residual disease following VEN-based treatment have further advanced prognostication capabilities and increased the ability for close disease monitoring and early targeted intervention prior to morphologic relapse. This review summarizes these recent developments and their impact on the treatment and survival of transplant-ineligible patients living with AML.
    Review • Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    Venclexta (venetoclax) • cytarabine • azacitidine
    11d
    Comprehensive Genomic Profiling (CGP) of Acute Myeloid Leukemias with Foundation One Heme Identifies Actionable Genomic Alterations and Biomarkers (ASH 2024)
    Current best practices for the diagnosis, classification, prognostication, and treatment of AML call for the assessment of the presence and absence of numerous genomic alterations. Therefore, in contrast to single-gene or small-panel molecular testing, the F1H platform can simplify such assessment via a CGP approach.
    IO biomarker
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • NUP214 (Nucleoporin 214) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MRTFA (Myocardin Related Transcription Factor A) • RBM15 (RNA Binding Motif Protein 15)
    |
    TP53 mutation • NPM1 mutation • KMT2A rearrangement • MLL rearrangement • U2AF1 mutation • CEBPA mutation • MLL mutation • NPM1 W288
    |
    FoundationOne® Heme CDx
    15d
    Case report: Triple-negative breast cancer with low tumour-infiltrating lymphocytes infiltration and good prognosis: a case of Tall Cell Carcinoma with Reversed Polarity and review of the literature. (PubMed, Front Oncol)
    TCCRP is a rare TNBC with inert biological behaviours and good prognosis. We found low infiltration of TILs in the pathological tissue of this case, which may be a characteristic of TCCRP, and the presence of Cancer-Associated Fibroblasts (CAF) in the interstitium of the tumour in this case may have suppressed the anti-tumour immunity to some extent, and further studies on the immune characteristics of the tumour microenvironment (TME) in TCCRP are needed.
    Review • Journal • Tumor-infiltrating lymphocyte • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
    |
    PIK3CA mutation
    17d
    The Validation of Digital PCR-based Minimal Residual Disease (MRD) Detection for the Common Mutations in IDH1 and IDH2 genes in Patients with Acute Myeloid Leukemia. (PubMed, J Mol Diagn)
    Controls and acceptable ranges were also established for each mutation during validation. This study suggests that the QuantStudio 3D Digital PCR assay is a quantitative, sensitive, and reproducible platform for monitoring MRD in AML patients.
    Journal • Minimal residual disease
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH1 mutation • IDH2 mutation • IDH2 R140Q
    19d
    Analysis of ASCL1/NEUROD1/POU2F3/YAP1 Yields Novel Insights for the Diagnosis of Olfactory Neuroblastoma and Identifies Sinonasal Tuft Cell-like Carcinoma. (PubMed, Mod Pathol)
    The therapeutic vulnerabilities associated with POU2F3 expression in SCLC suggest that a similar approach might be considered for POU2F3-positive carcinomas of the sinonasal tract. Given their diagnostic and possible therapeutic relevance, nNEM have potential to transform the way we approach the diagnosis and management of sinonasal small round epithelial/neuroepithelial malignancies.
    Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • YAP1 (Yes associated protein 1) • NCAM1 (Neural cell adhesion molecule 1) • POU2F3 (POU Class 2 Homeobox 3) • SYP (Synaptophysin) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)
    |
    IDH2 mutation • YAP1 positive
    20d
    Rapid intraoperative amplicon sequencing of CNS tumor markers. (PubMed, Comput Struct Biotechnol J)
    Our method achieved a turnaround time of 105 min at the point-of-care from receipt of a tumor biopsy to result with the potential to impact surgical strategy. Our approach can be integrated with recently developed DNA methylation-based diagnostic classification systems, corroborating diagnoses and even further specifying tumor grades, thus enabling a multimodal diagnostic intraoperative assessment of CNS malignancies.
    Journal
    |
    BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • H3-3A (H3.3 Histone A)
    |
    BRAF V600 • IDH1 R132 • IDH2 R172
    21d
    Exploring Extracellular Vesicle Surface Protein Markers Produced by Glioblastoma Tumors: A Characterization Study Using In Vitro 3D Patient-Derived Cultures. (PubMed, Cancers (Basel))
    This study underscores the efficacy of the tumor-derived explant model and its potential to advance the understanding of GBM biology and EV production. A key innovation is the isolation of EVs from a model that faithfully mimics the tumor's original cytoarchitecture, offering a deeper understanding of the cells involved in EV release. The identified EV surface markers represent promising targets for enhancing EV isolation and optimizing their use as diagnostic tools. Moreover, further investigation into their molecular cargo may provide crucial insights into tumor characteristics and evolution.
    Preclinical • Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation
    22d
    miR-200 family as new potential prognostic factor of overall survival of patients with WHO G2 and WHO G3 brain gliomas. (PubMed, Sci Rep)
    Members of the miR-200 family exhibit prognostic value for 2- and 5-year OS. Presented predictive models of survival may be clinically useful for treatment optimization.
    Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MIR200B (MicroRNA 200b) • MIR200C (MicroRNA 200c) • MIR429 (MicroRNA 429) • MIR200A (MicroRNA 200a) • MIR141 (MicroRNA 141) • MIR200 (MicroRNA 200)
    |
    miR-200-a expression • miR-141 expression • miR-200-c expression • miR-429 expression
    22d
    Novel Fibroblast Growth Factor Receptor 3-Fatty Acid Synthase Gene Fusion in Recurrent Epithelioid Glioblastoma Linked to Aggressive Clinical Progression. (PubMed, Curr Oncol)
    Postoperative treatment included radiotherapy and temozolomide...The recurrence was managed with regorafenib and bevacizumab, though complications like hand-foot syndrome and radiation necrosis arose...The novel FGFR3-FASN fusion suggests potential implications for GBM recurrence and lipid metabolism. Further studies are warranted to explore FGFR3-FASN's role in GBM and its therapeutic targeting.
    Journal
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    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FASN (Fatty acid synthase)
    |
    IDH2 mutation • PTEN deletion • PTEN mutation • CDKN2A deletion • CDKN2A mutation • TERT mutation • TERT promoter mutation
    |
    Avastin (bevacizumab) • temozolomide • Stivarga (regorafenib)
    22d
    Survey for Activating Oncogenic Mutation Variants in Metazoan Germline Genes. (PubMed, J Mol Evol)
    While cancer expansion ensues from dysregulated growth elicited by these mutations, this effect is likely detrimental to embryonic development and/or survival of multicellular organisms. Although all oncogenic mutations considered here are gain-of-function where five of the six increase activity of the encoded proteins, clonal advancement promotes tumor growth by these genomic changes without conferring selection advantages benefiting the organism or species.
    Journal
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2)
    |
    EGFR mutation • BRAF mutation • PIK3CA mutation
    23d
    Canonical Amplifications and CDKN2A/B Loss Refine IDH1/2-mutant Astrocytoma Prognosis. (PubMed, Neuro Oncol)
    Combining CDKN2A/B hemizygous-loss and focal gene amplifications reveals a group of IDHmut-astrocytoma patients with intermediate prognosis, refining IDHmut-astrocytoma classification.
    Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    24d
    Clinical and biological advances of critical complications in acute myeloid leukemia. (PubMed, Leuk Lymphoma)
    Venetoclax-induced TLS and differentiation syndrome (DS) from IDH1/IDH2 or menin inhibitors highlight the need for ongoing research and innovative approaches...Effective AML management relies on collaborative efforts from hematologists, specialized services, and intensive care units (ICUs). This review analyzes recent data on critical AML complications, identifies areas for further investigation, and proposes ways to advance clinical research and enhance patient care strategies.
    Review • Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    Venclexta (venetoclax)
    25d
    Impact of genetic alterations on long-term outcomes in resectable intrahepatic cholangiocarcinoma: meta-analysis. (PubMed, Br J Surg)
    Determining the overall prevalence of the most common actionable and undruggable mutations may help to expand target therapy indications in the adjuvant setting. Inconsistent results have been found for some infrequent gene alterations; their rare involvement could potentially bias their prognostic meaning.
    Clinical • Retrospective data • Review • Journal
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    KRAS mutation
    27d
    MYB::QKI fusion-positive diffuse glioma of the cerebellum: A case report. (PubMed, Neuropathology)
    Although the morphological findings and the presence of fusion indicated that the tumor was a cerebellar AG, the DNA methylome profile did not match that of AG. An accumulation of more cases is needed to determine the precise nature of the tumor, which may lead to an expansion of the tumor concept.
    Journal
    |
    BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • H3-3A (H3.3 Histone A) • GFAP (Glial Fibrillary Acidic Protein) • H3C1 (H3 Clustered Histone 1) • MYBL1 (MYB Proto-Oncogene Like 1) • OLIG2 (Oligodendrocyte Transcription Factor 2)
    |
    BRAF V600 • IDH1 R132H • IDH1 R132 • IDH2 R172
    28d
    Epigenetic and Immune Profile Characteristics in Sinonasal Undifferentiated Carcinoma. (PubMed, Cancer Med)
    Our study suggests epigenetic mechanisms, particularly via EZH2, play a crucial role in SNUC carcinogenesis. Furthermore, distinctive immune cell profiles in SNUC point to potential immune-related characteristics of this malignancy.
    Journal • IO biomarker
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    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD8 (cluster of differentiation 8) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • LAG3 (Lymphocyte Activating 3) • H3C1 (H3 Clustered Histone 1)
    |
    IDH2 mutation • LAG3 expression • IDH2 R172
    29d
    Cost-effectiveness of Enasidenib versus conventional care for older patients with IDH2-mutant refractory/relapsed AML. (PubMed, Leuk Lymphoma)
    The cost of ENA would need to be decreased by 72% to be cost-effective at a willingness-to-pay threshold of $150,000/QALY. Our findings suggest that ENA is unlikely to be a cost-effective treatment for older patients with IDH2-mutant R/R AML under current pricing.
    Journal • HEOR • Cost-effectiveness • Cost effectiveness
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation
    |
    Idhifa (enasidenib)
    29d
    Menin inhibitors for the treatment of acute myeloid leukemia: challenges and opportunities ahead. (PubMed, J Hematol Oncol)
    More importantly, approval of the combination of the BCl-2 inhibitor, venetoclax, and hypomethylating agents or low dose cytarabine provided unprecedented breakthrough for the frontline treatment of older, unfit AML patients. Recent development of menin inhibitors targeting AML with KMT2A rearrangements or NPM1 mutations could represent a promising new horizon of treatment for patients within these subsets of AML. Our current review will focus on a summary and updates of recent developments of menin inhibitors in the treatment of AML, on the challenges ahead arising from drug resistance, as well as on the opportunities of novel combinations with menin inhibitors.
    Review • Journal • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
    |
    NPM1 mutation • KMT2A rearrangement • MLL rearrangement
    |
    Venclexta (venetoclax) • cytarabine
    30d
    Proton pump inhibitors are detrimental to overall survival of patients with glioblastoma: Results from a nationwide real-world evidence database. (PubMed, Neurooncol Pract)
    ALDH1A1 is a primary metabolic enzyme impacting the outcome of chemotherapy, including temozolomide...Evidence from a nationwide cancer registry has suggested PPIs have a negative impact on OS for GBM patients, particularly those with MGMT promoter methylation. This suggests PPIs should be avoided for prophylactic management of gastrointestinal toxicity in patients with GBM receiving chemoradiotherapy.
    Journal • HEOR • Real-world evidence • Real-world
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1)
    |
    MGMT promoter methylation
    |
    temozolomide
    1m
    Outcomes of patients with acute myeloid leukemia and bone marrow fibrosis. (PubMed, J Hematol Oncol)
    In a multivariate analysis, grade 2-3 MF (HR 2.0, 95%CI 1.59-2.51) was the strongest prognostic factor for survival. In summary, grade 2-3 MF in AML is associated with worse outcomes.
    Retrospective data • Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    JAK2 mutation
    1m
    Multi-omics-driven discovery of invasive patterns and treatment strategies in CA19-9 positive intrahepatic cholangiocarcinoma. (PubMed, J Transl Med)
    This study systematically elucidated the clinical, genomic, transcriptomic, and immune features of CA19-9 positive ICC. It reveals glycolysis-associated cellular communities and their cancer-promoting mechanisms, enhancing our understanding of ICC and laying the groundwork for individualized therapeutic strategies.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CA 19-9 (Cancer antigen 19-9) • SLC2A1 (Solute Carrier Family 2 Member 1)
    |
    KRAS mutation
    1m
    IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma. (PubMed, Target Oncol)
    A significant number (50-80%) of chondrosarcomas have a mutation in the isocitrate dehydrogenase (IDH) genes. This review focuses on IDH-mediated pathogenesis and recent pharmacological advances with novel IDH inhibitors, explores their potential therapeutic value, and proposes potential future avenues for clinical trials combining IDH inhibitors with other systemic agents for chondrosarcomas.
    Review • Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    1m
    Isocitrate dehydrogenase 2 mutation promotes cytarabine resistance in acute myeloid leukemia by Warburg effect. (PubMed, Hematol Oncol)
    To investigate cellular responses, the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) was administered to the cells...The increase in glycolysis levels following IDH2 mutation may contribute to the reduced efficacy of Enasidenib in inhibiting the proliferation of IDH-mutant AML cells...BEZ235 significantly inhibits the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), mTOR, glycolytic metabolism, and Ara-C resistance both in vitro and in vivo. Overexpression and mutation of IDH2 coordinate with the Warburg effect through the PI3K/Akt/mTOR pathway to promote Ara-C resistance in AML.
    Journal
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    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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    IDH2 mutation • IDH2 overexpression
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    cytarabine • dactolisib (RTB101) • Idhifa (enasidenib)
    1m
    NCI-2018-00876: Telaglenastat With Radiation Therapy and Temozolomide in Treating Patients With IDH-Mutated Diffuse Astrocytoma or Anaplastic Astrocytoma (clinicaltrials.gov)
    P1, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Combination therapy
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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    IDH1 mutation • IDH2 mutation
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    temozolomide • telaglenastat (CB-839)
    1m
    In vivo models of subclonal oncogenesis and dependency in hematopoietic malignancy. (PubMed, Cancer Cell)
    We next use a generalizable, reversible approach to demonstrate that mutation reversion results in rapid leukemic regression with distinct differentiation patterns depending upon co-occurring mutations. These studies provide a path to experimentally model sequential mutagenesis, investigate mechanisms of transformation and probe oncogenic dependency in disease evolution.
    Preclinical • Journal
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    FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
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    FLT3 mutation • NPM1 mutation • DNMT3A mutation
    1m
    Genetic, Epigenetic, and Microenvironmental Drivers of Cholangiocarcinoma. (PubMed, Am J Pathol)
    This review explores the multifaceted genetic, epigenetic and microenvironmental drivers of CCA. Understanding these diverse mechanisms is essential for characterizing the complex pathways of CCA carcinogenesis and developing targeted therapies to improve patient outcomes.
    Review • Journal
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    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)
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    IDH1 mutation • ARID1A mutation • FGFR2 mutation • BAP1 mutation
    1m
    Diagnostic and Clinical Utility of OncoScan Microarray and NGS-Based Sequencing in Pediatric Solid Tumors: Children's Mercy Hospital Experience (AMP 2024)
    OS+ is a reliable test to identify clinically relevant genomic alterations, cnLOH, and several hotspot mutations in pediatric FFPE solid tumor specimens. WGS/WES significantly increases the yield of actionable somatic mutations and cancer-predisposing germline variants. The cost, turnaround time, and tumor percentage in the specimen make OS+ followed by WES principal tests for pediatric solid tumor analysis at our institution.
    Clinical • Next-generation sequencing
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • H3-3A (H3.3 Histone A)
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    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • PIK3CA mutation • BRAF V600 • PTEN mutation • BRAF fusion
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    OncoScan™ CNV Assay
    1m
    Rapid Determination of IDH1 and IDH2 Mutation Status in AML and Glioma Using a Microfluidic Detection System (AMP 2024)
    Determination of IDH1-2 mutation status is important for a variety of malignancies for diagnostics, classification, prognosis, and therapy selection. The Idylla system is easy to use and requires little training; therefore, it is the ideal assay to implement in a variety of labs. Overall, the Idylla platform provides quick, dependable, and easy-to-use technology for performing this analysis.
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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    IDH1 mutation • IDH2 mutation • KIT mutation
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    Idylla™ IDH1-2 Mutation Assay
    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
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    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)
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    KRAS mutation • BRAF mutation • IDH wild-type • IDH1 R132 • IDH2 R140Q • IDH1 R132L • IDH2 R140 • IDH2 R172
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    MSK-IMPACT
    1m
    Performance Assessment and Clinical Validation of the Idylla IDH1-2 Mutation Assay Kit in Rapid Detection of IDH Mutations in Acute Myeloid Leukemia (AMP 2024)
    The Idylla IDH1-2 Mutation Assay Kit performed on the Biocartis Idylla system demonstrated a rapid and cost-effective alternative to the standard approaches. This assay can be used to evaluate clinically relevant IDH variants in a much shorter turnaround time and from limited biological samples, which makes this a preferred technique to develop clinical tests for diagnosis, prognosis, and evaluation of treatment in AML.
    Clinical
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    KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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    IDH1 mutation • KIT mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH2 R172
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    Idylla™ IDH1-2 Mutation Assay
    1m
    DNA and RNA NGS for Myeloid Neoplasms Using Oncomine Myeloid Assay GX v2 on GeneXus: An Assessment of Clinical Utility (AMP 2024)
    This DNA- and RNA-based 80-gene panel has proven to be a powerful tool for genomic profiling of myeloid neoplasms. The results were provided to hematopathologists/oncologists in timely fashion with the critical information for diagnosis confirmation, and disease classification, as well as assessment of patient response to treatment.
    Clinical • Next-generation sequencing
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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    FLT3-ITD mutation • NPM1 mutation • U2AF1 mutation • CEBPA mutation • JAK2 V617F
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    Oncomine Myeloid Assay GX
    1m
    Target-Capture Next-Generation Sequencing (NGS) for Use in Molecular-Based Research of Myeloid Measurable Residual Disease (MRD) (AMP 2024)
    Target-capture NGS provides the opportunity to evaluate many genes in a single assay. Suitability for MRD requires highly uniform and sensitive target enrichment. Our study demonstrated reliable and accurate detection of variants down to 0.05% VAF, providing researchers with the capability to use capture-based NGS for myeloid MRD monitoring.
    Next-generation sequencing
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2)
    |
    FLT3-ITD mutation • NPM1 mutation • FLT3 D835Y • FLT3 D835 • IDH2 R172K • KIT D816V • IDH1 R132C • JAK2 V617F • IDH1 R132 • IDH2 R172
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    SureSeq™ Myeloid MRD Panel
    1m
    Evaluation of Performance of the Idylla IDH1/2 Mutation Assay Using Direct Whole Blood and Bone Marrow (AMP 2024)
    These mutations are targetable using agents such as ivosidenib and vorasedinib in AML... The Biocartis Idylla IDH1-2 mutation assay shows good concordance with ddPCR and an LOD of 2.5% VAF. Though the analytical sensitivity of this assay is lower than ddPCR, this may not be a limitation in acute, newly diagnosed patients presenting with increased blast counts. This assay offers the advantage of direct specimen testing for PB and BM without DNA extraction with faster turnaround time than other methods.
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH1 mutation • IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH2 R140Q • IDH2 R140 • IDH2 R172
    |
    Idylla™ IDH1-2 Mutation Assay
    |
    Tibsovo (ivosidenib)
    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)