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    BIOMARKER:

    IDH2 R172G

    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
    Entrez ID:
    3418
    Related biomarkers:
    Expression
    Mutation
    Others
    Related tests:
    1year
    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)
    1year
    Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations (clinicaltrials.gov)
    P2, N=145, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132L • IDH1 R132S • IDH1 R132V • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)
    almost2years
    Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations (clinicaltrials.gov)
    P2, N=145, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132L • IDH1 R132S • IDH1 R132V • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)
    almost2years
    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=94, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    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)
    2years
    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=94, Recruiting, National Cancer Institute (NCI) | Active, not recruiting --> Recruiting
    Enrollment open
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)
    2years
    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=94, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)
    over2years
    Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations (clinicaltrials.gov)
    P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH1 R132H • IDH2 R172K • IDH1 R132C • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)
    almost3years
    IDH2-Mutated Sinonasal Tumors: A Review. (PubMed, Adv Anat Pathol)
    One-, 3- and 5-year survival rates are 83%, 50%, and 43%, respectively. In all but 1 study, IST is associated with better outcomes than IDH2 wild-type tumors and SMARCB1-deficient sinonasal tumors.
    Review • Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
    |
    IDH2 mutation • IDH wild-type • IDH2 R172 • IDH2 R172G
    almost3years
    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=94, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
    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 • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)
    3years
    Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2. (PubMed, Sci Rep)
    Using overlapping PCR, transfection, immunoblotting, immunoprecipitation, measurements of enzyme activity, glucose, lactic acid, ATP, and reactive oxygen species (ROS), cell viability, protein degradation assays post-inhibition of the 26S proteasome (bortezomib) or HSP90 (17-AAG), and a homology model, we demonstrated that the properties of ten cancer-associated IDH2 variants (R140G/Q/W and R172S/K/M/W/G/C/P) arising from point mutations are closely related to their structure and stability...The homology model further revealed that changes in conformation and IDH2 protein stability appeared to be associated with these point mutations. Taken together, our findings provide information important for understanding the molecular mechanisms of IDH2 mutations in tumors.
    Journal
    |
    IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CCND1 (Cyclin D1) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    IDH2 mutation • IDH2 R172K • CCND1 expression • IDH wild-type • IDH2 R140Q • IDH2 R140 • IDH2 R172 • IDH2 R172G • IL6 expression • IDH2 overexpression
    |
    bortezomib
    over3years
    Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations (clinicaltrials.gov)
    P2, N=145, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2022 --> Jul 2023 | Trial primary completion date: Jul 2022 --> Jul 2023
    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 • IDH1 R132 • IDH1 R132G • IDH2 R140Q • IDH1 R132V • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)
    over3years
    Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma. (ASCO 2022)
    Olaparib was well tolerated in this pt population. The study did not meet the pre-specified response-based threshold for moving to step 2, but prolonged SD was observed in pts with grades 2 and 3 histologies, suggesting olaparib monotherapy could be of clinical benefit in select pts. Grade 4 tumors per the 2021 WHO classification defined by histology or CDKN2A mutation derived minimal to no benefit from this drug highlighting the usefulness of this new classification for future patient stratification and trial design and suggesting investigation of this treatment earlier in the disease course might be of interest.
    Clinical • P2 data • BRCA Biomarker • PARP Biomarker
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
    |
    IDH1 mutation • IDH2 mutation • CDKN2A deletion • CDKN2A mutation • IDH1 R132H • IDH2 R172K • IDH1 R132 • IDH2 R172 • IDH2 R172G
    |
    Lynparza (olaparib)