IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

P=N/A, N=450, Completed, West China Hospital

This review compared the efficacy and safety of low-dose cytarabine (LDAC), azacitidine (AZA), 5- and 10-day decitabine (DEC), and gemtuzumab ozogamicin, alone or combined with drugs such as venetoclax (VEN), in older adults with AML ineligible for conventional chemotherapy. Treatment decisions should consider patient goals and functional status. These findings informed eight recommendations in updated ASH-AML guidelines.

Overall, dapolsertib demonstrated modest single-agent activity in patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT03008187.

Molecular testing has become an essential component of modern iCCA management. Broad, early, and technically integrated molecular profiling-ideally performed at initial diagnosis and interpreted in an interdisciplinary (molecular) tumor board-is critical to fully realize the potential of precision oncology in BTC.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.

P1, N=30, Not yet recruiting, Servier Bio-Innovation LLC | Initiation date: Sep 2025 --> Jan 2026

Interestingly, C269 autopalmitoylation occurs within a hydrophobic pocket, targeted by a clinical IDH1-mutant inhibitor (LY3410738). Our study reveals that autopalmitoylation, conferred by the IDH1R132H mutation, links fatty acid metabolism to the regulation of IDH1 mutant activity and represents a druggable vulnerability in IDH1-mutant cancers.

P2, N=103, Recruiting, Alpheus Medical, Inc. | Not yet recruiting --> Recruiting

In the AVALON cohort of relapsed/refractory AML treated with venetoclax plus hypomethylating agents, NPM1 and IDH1/2 mutations showed no significant impact on response or survival. These findings indicate that prognostic models for relapsed AML should consider treatment context rather than baseline mutation status.

We further identify critical research gaps, including single-cell and spatial mapping of TET/5hmC dynamics, microenvironmental regulation of TET activity, functional cooperation between TET isoforms, and the development of clinically feasible delivery systems and biomarkers. Addressing these challenges will be essential to translate TET pathway modulation into effective, individualized combination therapies for glioma patients.

Mechanistically, the dual IDH1/ATRX alteration upregulates pro-ferroptotic genes (HMOX1 and ACSL4) while downregulating anti-ferroptotic genes (SLC7A11 and GPX4), thereby sensitizing GBM cells to ferroptosis induction. Together, our findings provide new biological insights into IDH1/ATRX-driven GBM pathogenesis and highlight ferroptosis as a potential therapeutic vulnerability in this aggressive tumor subtype.

The IDH1-wt group showed higher amplitude of MMN evoked by novel stimulus at Fz and Cz and longer latency of the P300 component evoked by a deviant stimulus at Fz. The combination of AERP parameters yielded a more effective means to predict IDH1 mutation status in patients with insular glioma, which may provide guidance for the surgical intervention of this disease.