IDH1 R132

The clinical value of IDH and ATRX mutations in prognostic assessment was confirmed (p ≤0.05). The overexpression of p53 had no significant impact on OS (p = 0.726). Therefore, p53 alone cannot predict survival in glioblastoma patients. Based on the results, these biomarkers may be a potential therapeutic target to prolong patient survival, hence the need for further investigations.

The pH-based colorimetric indicator of LNA-LAMP facilitates convenient visual interpretation of reactions, and we demonstrate successful translation to an end-point format using absorbance ratio, allowing for an alternative and objective approach for differentiating between positive and negative reactions. Importantly, the LNA-LAMP genotyping panel is highly reproducible, with no false-positive or false-negative results observed.

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.

Importantly, pharmacological blockage of DNA methylation or IDH1-R132H mutant and CD47/SIRPα signaling synergistically enhances TAM-based phagocytosis and glioma elimination in vivo. Our findings unveil a general mechanism by which NSUN5/TET2/RBFOX2 signaling regulates RNA metabolism and highlight NSUN5 targeting as a potential strategy for glioma immune therapy.

The U.S. Food and Drug Administration (FDA) approved Ivosidenib, a molecular entity that targets IDH1 with R132 mutations, as a promising therapeutic option for AML with mIDH1 in 2018...RMSD showed that the four dynamics simulation systems remained stable, and RMSF and Rg showed that the screened molecules have similar local flexibility and tightness to the positive drug. Finally, the lowest energy conformation, hydrogen bond analysis, and free energy decomposition results indicate that in the entire system the key residues LEU120, TRP124, TRP267, and VAL281 mainly contribute van der Waals forces to the interaction, while the key residues VAL276 and CYS379 mainly contribute electrostatic forces.

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.

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P2/3, N=147, Active, not recruiting, National Cancer Institute (NCI) | N=485 --> 147 | Trial completion date: Aug 2024 --> Mar 2025 | Trial primary completion date: Aug 2024 --> Apr 2023

No abstract available

With advancements in molecular diagnostics and precision therapy, IDH inhibitors such as ivosidenib, vorasidenib and enasidenib are now mainstay in management of patients with a susceptible mutation. The Idyllaâ„¢ IDH1-2 Mutation Assay Kit (RUO) is a fully automated qPCR assay for the qualitative detection of 15 common mutations in IDH1 (R132C/H/G/S/L) and IDH2 (R140Q/L/G/W, R172K/M/G/W/S) at codon level. The Idyllaâ„¢ IDH1-2 Mutation Assay Kit demonstrates a high concordance with established reference methods across a range of different specimen types.

P1, N=49, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: May 2024 --> May 2025

P1, N=166, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2024 --> Oct 2025

In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness...TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.

P1/2, N=336, Completed, Forma Therapeutics, Inc. | Active, not recruiting --> Completed

P1, N=75, Recruiting, Hutchmed | Trial completion date: Sep 2023 --> Jun 2025 | Trial primary completion date: Sep 2023 --> Sep 2024

We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.

P1/2, N=60, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Suspended --> Completed

GBs with detectable ALK-protein expression could potentially experience substantial clinical advantages through the utilization of newly introduced ALK inhibitors allowing personalized treatment to a subset of patients. Hence, future studies targeting ALK in IDH wildtype Glioblastomas including clinical trials on larger scales are recommended.

P2, N=145, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

Additionally, IDH1 R132H mutation predicted higher seizure-free ratios in LGG patients with intact ATRX expression (OR = 6.793, 95%CI = 1.217 - 37.923, P = 0.029) one year after diagnosis. Therefore, our findings suggest that IDH1 mutation can predict seizure occurrence and control in LGG patients, providing further insights into the relationship between glioma and epilepsy.

This is the first known report of skull base periosteal chondroma. Genetic testing was useful for confirming the diagnosis, and EES was effective for treatment. Should such a tumor show adhesion to an important structure, an intracapsular excision can be beneficial for avoiding complications.

No IDH2 mutations were found. The use of independent diagnostic methods may improve the detection of IDH-mutant specimens in chondroid tumors.

The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

These neo-T cells could selectively recognize and kill HLA-matched AML targets endogenously expressing IDH2R140Q both in vitro and in vivo. Overall, our findings support the clinical translation of neoantigen-specific T cells to treat R/R AML.

Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.

P1/2, N=70, Recruiting, Washington University School of Medicine | Trial completion date: Jan 2030 --> Jan 2032 | Trial primary completion date: Jan 2030 --> Jan 2032

The present study demonstrates that liquid biopsy may be used in brain tumors to detect IDH1 mutation which represents an important prognostic biomarker in patients with different types of gliomas, being associated to OS.

P3, N=560, Recruiting, CarThera | Not yet recruiting --> Recruiting

We found that IDH1 R132 mutations were negatively associated with the prognosis of patients with bone chondrosarcomas. Nevertheless, more extensive studies (such as multicenter international studies) are needed and advisable to confirm our observations in this preliminary small series. Moreover, evaluating mutational status in fresh samples instead of in paraffin-embedded sections could help to increase the number of patients with adequate DNA for analysis. If our findings will be confirmed, the evaluation of IDH mutational status in biopsy samples or resection specimens could be considered when stratifying patients, highlighting those who may benefit from more aggressive treatment (such as adjuvant chemotherapy) or closer follow-up.

P1/2, N=92, Recruiting, Servier Bio-Innovation LLC

P1/2, N=336, Active, not recruiting, Forma Therapeutics, Inc.

P1/2, N=57, Recruiting, Northwestern University

MB isolation had a higher yield than CB isolation (P<0.0001), and post-isolation vacuum increased the final concentration in both methods, with little effect on cfDNA integrity. Our study provides a protocol to maximize CSF-ctDNA concentrations in IVD testing and future studies.

P2, N=25, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial primary completion date: Sep 2023 --> Mar 2023

Taken together, we provide proof for the potential of our sCSC technology as a potent addition to biomarker-driven drug development projects or studies on tumor therapy resistance. Moreover, follow-up projects such as comparing in vitro drug sensitivity profiles of hiPSC-derived tissue progenitors of different lineages, might help to understand a variety of tissue-related functions of IDH1 mutations.

P3, N=220, Recruiting, Servier Affaires Médicales | Phase classification: P3b --> P3

P1/2, N=60, Suspended, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Oct 2023 --> Dec 2023 | Trial primary completion date: Oct 2023 --> Dec 2023

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

In conclusion, post-HCT maintenance therapy with enasidenib is safe and feasible with highly favorable survival outcomes in mIDH2 AML. Treatment delays and dose reductions were commonly seen; however, most patients completed their 2-years maintenance.

P3, N=331, Active, not recruiting, Institut de Recherches Internationales Servier

Baseline bone blast count was strongly predictive of response to treatment. Further evaluation of these observations is needed.

P2, N=16, Completed, Jason J. Luke, MD | Recruiting --> Completed | N=35 --> 16 | Trial completion date: May 2026 --> Nov 2023 | Trial primary completion date: Mar 2024 --> Nov 2023