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GENE:

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

News alerts, weekly reports and conference planners

The Prognostic Value of Integrating Copy Number Alteration Profiles in NPM1-Mutated Acute Myeloid Leukemia: An Exploratory Study. (PubMed, Appl Clin Genet)

This exploratory study suggests that combining CNAs and gene mutation profiles may potentially improve the existing prognostic evaluation system for NPM1-mutated AML patients. Confirmation of these results requires additional validation in larger prospective cohorts.

1 day ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)

FLT3-ITD mutation • NPM1 mutation

Contemporary Precision Stratification and Prognostic Features of Primary Gliomas in a Southern Chinese Population. (PubMed, Research (Wash D C))

Contemporary glioma cohorts showed prolonged survival outcomes compared to historical cohorts. An association between anatomic localization and molecular subtypes was also established in this Chinese glioma cohort.

1 day ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH wild-type

Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov)

P1, N=27, Recruiting, Washington University School of Medicine | N=12 --> 27

2 days ago

Enrollment change

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase)

IDH2 mutation • MGMT promoter methylation • IDH wild-type

Zynyz (retifanlimab-dlwr) • neoantigen DNA vaccine

Tall cell carcinoma with reversed polarity: case report of a rare special type of breast cancer and review of the literature. (PubMed, Discov Oncol)

This case underscores the importance of integrating histomorphological features, immunohistochemical profiles, and molecular biomarkers to distinguish TCCRP from other triple-negative breast carcinomas. Recognition of this indolent entity is critical for avoiding overtreatment and ensuring appropriate clinical management, given its favorable prognosis compared to conventional triple-negative breast cancers.

4 days ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TP63 (Tumor protein 63) • GATA3 (GATA binding protein 3)

HER-2 expression • IDH2 R172

PARP inhibitor resistance in IDH1-mutant cancers due to loss of end protection factors, 53BP1 and REV7. (PubMed, NAR Cancer)

To overcome this resistance, we found that treatment with the receptor tyrosine kinase inhibitor, cediranib, previously reported to suppress expression of downstream HDR factors, resensitizes 53BP1 and REV7-knockout cells to PARPi treatment. Our findings identify key pathways driving PARPi resistance in IDH1-mutant cancers and highlight potential therapeutic strategies to overcome this resistance.

4 days ago

Journal • PARP Biomarker

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

IDH1 mutation

Recentin (cediranib)

ACSL5 Regulates Glucose Metabolism and Chemotherapy Sensitivity in Colorectal Cancer Cells under Glutamine Deficiency. (PubMed, Adv Sci (Weinh))

Nonetheless, these metabolic increases also generate reactive oxygen species (ROS), inducing DNA damage and significantly enhancing colorectal cancer cell sensitivity to oxaliplatin. The latter provides an explanation as to why colorectal tumors with high ACSL5 expression display preferentially improved patient outcomes from chemotherapy. Collectively, the findings reveal a new pathway for non-genetic chemotherapy resistance mechanisms, deepen the understanding of metabolic reprogramming in tumor cells, and offer potential therapeutic targets for future treatment strategies.

4 days ago

Journal

TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MDM2 (E3 ubiquitin protein ligase) • ACSL5 (Acyl-CoA Synthetase Long Chain Family Member 5)

oxaliplatin

Metabolic and epigenetic dysregulation in IDH1/2-mutant gliomas: A microglial-mediated mechanism of blood-brain barrier disruption. (PubMed, Int Immunopharmacol)

This review aims to comprehensively examine the association between IDH1/2 mutations and BBB disruption, elucidating how IDH1/2-mutant gliomas alter tumor-associated metabolic and epigenetic pathways, which subsequently influence microglial activation and polarization, contributing to BBB impairment. Furthermore, we propose that microglia-mediated BBB disruption may be one of the underlying mechanisms contributing to complications in IDH1/2-mutant gliomas, such as vasogenic edema and immune-mediated encephalopathy, both of which are closely associated with BBB breakdown.

7 days ago

Review • Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

IDH wild-type

Targeted triplet therapies incorporating FLT3 or IDH inhibitors: ready for prime time? (PubMed, Hematology Am Soc Hematol Educ Program)

Triplet therapies combining hypomethylating agents, venetoclax, and targeted inhibitors are emerging as a promising therapy for older patients with AML unfit for intensive chemotherapy...While effective, the need to remain on indefinite therapy for individuals who are not stem cell transplant candidates and dose optimization/de-escalation strategies remain critical concerns. Herein, we aim to review the current treatment landscape of newly diagnosed and relapsed/refractory FLT3- and IDH1/2-mutated AML and the role of triplet regimens in these molecular subgroups.

7 days ago

Review • Journal

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

FLT3-ITD mutation • IDH1 mutation

Venclexta (venetoclax)

Metabolic reprogramming of CAR T cells: a new frontier in cancer immunotherapy. (PubMed, Front Immunol)

In conclusion, metabolic engineering, leveraging its impact on epigenetic regulation during CAR T cell manufacturing, is crucial for generating potent, persistent, and functionally resilient products. This approach holds immense promise for expanding the curative potential of CAR T cell therapy to a broader range of cancers, particularly challenging solid tumors.

7 days ago

Review • Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ACAT1 (Acetyl-CoA Acetyltransferase 1) • IL15 (Interleukin 15) • IL21 (Interleukin 21) • IL7 (Interleukin 7)

Frequency and impact of somatic co-occurring mutations on post-transplant outcomes in acute myeloid leukemia: a multicenter registry analysis on behalf of the EBMT ALWP. (PubMed, Bone Marrow Transplant)

OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.

8 days ago

Journal

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) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

TP53 mutation • FLT3-ITD mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation

Beyond the genome: epigenetic regulation of immune responses and T cells in brain tumors. (PubMed, Front Immunol)

To our knowledge, this is among the first comprehensive reviews to integrate CNS-specific immune privilege mechanisms with peripheral exhaustion pathways, providing a unified perspective on how epigenetic regulation orchestrates immune dysfunction across central and peripheral contexts. By mapping the continuum between immune evasion and global immunosuppression, we propose a conceptual framework for tailoring epigenetic-immunotherapy combinations to achieve durable antitumor immunity in the CNS.

8 days ago

Review • Journal • IO biomarker

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)

11d

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

11 days ago

Trial completion date • Trial termination • Pan tumor • Platinum sensitive

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 • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation

Zejula (niraparib) • Jemperli (dostarlimab-gxly)