IDH1 mutation

A clinical radiomics-integrated model that combined qBOLD parametric maps, CE-T1W, and T2W images with age achieved promising performance for predicting IDH1 mutation in glioma patients.

Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine. Median duration of CRc and ORR: 13.15 (range: 2.4-48.7) and 14.3 months (range: 2.4-48.7), respectively, and median overall survival: 13.8 months (95% confidence interval: 3.70-23.7). Olutasidenib demonstrated encouraging response rates with a manageable safety profile for patients with post-MPN mIDH1 AML.

P2, N=27, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P1, N=81, Completed, Bayer | Active, not recruiting --> Completed

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.

Representative drugs selected for further investigation included docetaxel, methotrexate, panobinostat, idarubicin, camptothecin, and pevonedistat. In conclusion, we identified several highly effective agents with potent anti-tumor activity in chondrosarcoma cells, independent of IDH mutation status. These agents represent promising candidates for chondrosarcoma therapy and warrant further preclinical investigation and potential inclusion in clinical trials.

The responsiveness of gastrointestinal stromal tumors to imatinib requires validation via molecular testing. Patients diagnosed with pancreatic cancer may see enhanced survival rates by targeted therapy addressing microsatellite instability and BRCA mutations. In bile duct malignancies, especially intrahepatic cholangiocarcinoma of the small duct variant, the analysis of IDH1 mutations and FGFR2 fusions presents new treatment prospects.

Different subtypes of IDH mutations may lead to different AML prognoses, suggesting the feasibility of personalized treatment for AML patients.

A high-throughput screening of 221 anti-cancer drugs identified five candidates-bortezomib, carfilzomib, doxorubicin, panobinostat, and romidepsin-that demonstrated low IC50 values, indicating potential efficacy in treating CS. These findings suggest that NCC-CS1-C1 is a valuable tool for both preclinical and basic research on high-grade conventional central CS.

It also identified a high frequency (17%) of SPOP gene mutations in Jordanian Arab PCa patients, mainly in exon 7. No IDH1 mutations were detected in exon 6.

Additionally, tissue microarrays from glioma patients at Tiantan Hospital showed significantly higher FCGR3A protein expression in high-grade gliomas compared to low-grade gliomas. In conclusion, our findings suggest that FCGR3A and FGL2 could serve as promising prognostic biomarkers and potential therapeutic targets for glioma patients.

IDH1-mutant CCA is characterized by increased abundance of M2-like TAMs. Targeting CCL2 remodels the tumor immune microenvironment and improves outcomes in preclinical models of IDH1-mutant CCA, highlighting the role for myeloid-targeted immunotherapies in the treatment of this cancer.

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.

A dual adeno-associated virus split intein system was used to successfully deliver the base editor in vitro and in vivo. Taken together, our study provides a strategy for a precise genetic intervention to target the IDH1 R132H mutation, enabling the development of accurate models to study its impact on glioma biology and serving as a framework for an in vivo gene therapy.

TP53 R248Q mutation increased cell adhesion to various substrates and significantly promoted cell migration on hyaluronic acid and chondroitin sulfate but did not change the migration rates on laminin and collagens IV and I. A double-mutant genotype produced by consequently introducing IDH1 R132H and TP53 R248Q to parental glioblastoma cells was characterized by the highest migration among all the cell lines, with particularly faster motility on chondroitin sulfate. These findings underscore the complex interactions between glioma cells, with the most important driver mutations and specific ECM components regulating cancer cell migration, offering valuable insights for potential therapeutic targets in glioma treatment.

ASXL1 mutation and low CD45RA+CD4+ T-cell counts correlated with progression to thrombocytopenia. Our findings underscore the clinical significance of thrombocytopenia dynamics in MF progression and prognosis, with implications for patient management and therapeutic interventions.

The FGFR and IDH-1 pathways are the primary targets for therapy, with FGFR-2 and IDH-1 inhibitors, such as Pemigatinib and Ivosidenib respectively, already available on the market. This prospective study validates the prevalence of mutations documented in the literature and underscores the significance of NGS in presenting supplementary therapeutic avenues. Moreover, we demonstrated the role of other potential targets co-expressed with FGFR2 or IDH1 which could represent a crucial opportunity for novel combinations or sequences therapies.

Among pts with EMP available, 64.2% had intrahepatic cholangiocarcinoma and 69.8% received CT1 (36.1% cisplatinum-gemcitabine). Despite a broader availability of EMP in advanced BTC in recent years, access to TT remains suboptimal even in referral Institutions. Our results demonstrate TT administration as a pivotal positive prognostic factor in a real-world setting, whilst FGFR2 or IDH1 alterations did not act as prognostic determinants per-se. Therefore, strategies aiming at improving the rate of patients receiving TT are warranted.

In present study, compounds M1, M2, M3 and M6 generated by BRNN exhibited optimal binding properties. This study is the first attempt to use deep learning to design mIDH1 inhibitors, which provides theoretical guidance for the design of mIDH1 inhibitors.

Molecular characterization of glioma is an important step in modern glioma diagnostics and immunohistochemistry can play an important role. IDH-1 mutation is commonly observed in adults, frontal lobe location, patients presenting with seizures, and WHO grade 2 tumors with the highest frequencies in oligodendrogliomas. ATRX and p53 can be used as surrogate markers for tumors of astrocytic lineage.

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

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.

This study identifies NDUFA6 and SDHA as novel companion prognostic biomarkers which might present a rational strategy for personalized therapy of AML patients.

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.

OCA Plus supports comprehensive detection of relevant copy number alterations in cancer FFPE samples. Combined with small variant profiling, detection of MSI, TMB, and HRD, OCA Plus facilitates comprehensive analysis of DNA structural changes in cancer that are relevant to precision oncology research.

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.

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.

P2, N=60, Not yet recruiting, Rigel Pharmaceuticals | Initiation date: Jun 2024 --> Nov 2024

These preliminary results suggest that CSF liquid biopsy may be useful for identifying mutations in primary and metastatic brain tumors. Serial sampling is feasible, and may disclose changes in diagnostic and/or driver mutations over time, with important therapeutic and diagnostic implications. Many mutations were found in CSF alone.

These preliminary results suggest that CSF liquid biopsy may be useful for identifying mutations in primary and metastatic brain tumors. Serial sampling is feasible, and may disclose changes in diagnostic and/or driver mutations over time, with important therapeutic and diagnostic implications. Many mutations were found in CSF alone.

For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD for increased post-transplant relapse risk.

Immunofluorescence showed that the genes from the unique cluster identified in the mutant growth plates were expressed in multiple growth plate anatomic zones, and pseudo-time analysis also suggested these cells could arise from multiple growth plate chondrocyte subpopulations. This data supports the notion that a subpopulation of chondrocytes become enchondromas at the expense of contributing to longitudinal growth.

The most common (≥20%) adverse reactions were nausea, fatigue, arthralgia, leukocytosis, dyspnea, pyrexia, rash, mucositis, diarrhea, and transaminitis. An assessment of long-term safety of olutasidenib is a condition of this approval.

This study revealed a correlation between SVZ contact in GBM and specific molecular markers, specifically IDH1 mutation, ATRX loss, and tumor size. SVZ contact could serve as criterion for categorizing GBMs, thus contributing to an improved understanding of the disease and potential therapeutic interventions.

P1, N=180, Recruiting, AstraZeneca | N=120 --> 180 | Trial completion date: Apr 2026 --> Sep 2026 | Trial primary completion date: Apr 2026 --> Sep 2026

P1, N=48, Not yet recruiting, Katy Peters, MD, PhD | Trial completion date: Aug 2027 --> Aug 2029 | Trial primary completion date: Aug 2025 --> Aug 2027

The present study suggests that CDKN2A deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant IDH1/2, they may have poor clinical outcomes because of CDKN2A deletion.

Among patients with advanced BTC, ctDNA-based genotyping showed acceptable concordance with tissue genomic profiling. Liquid biopsy using ctDNA could be a valuable complement to tissue-based genomic analysis in BTC.

Co-occurrence analysis revealed that the latest research focus of GRE were awake craniotomy, immunotherapy, cognitive impairment, and basic research on pathogenesis, with particular emphasis on the IDH1 mutation. This study intended to gain a deeper understanding of the current global GRE research and identify hotspots, as well as to provide theoretical reference for further studies.

P1, N=9, Terminated, AnHeart Therapeutics Inc. | N=63 --> 9 | Trial completion date: May 2026 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Aug 2025 --> Aug 2024; Sponsor adjusted the study strategy

P1/2, N=49, Recruiting, Neonc Technologies, Inc. | Trial primary completion date: Jun 2024 --> Dec 2024

In biochemical studies, olutasidenib selectively inhibits mutant but not wild-type IDH1, whereas ivosidenib appears to potently block both mutant and wild-type IDH1. Although they have the same target, olutasidenib and ivosidenib have unique molecular features, which may translate to selectivity differences in their inhibitory activity against IDH1.