IDH1 R132

Real-world data from our cohort and the TriNetX database support the oncological outcomes reported in the ClarIDHy trial and other real-world cohorts.

In this hospital-based cross-sectional study, IDH1 (R132H) IHC-negative status was more frequently observed in higher-grade tumors. These findings support the use of immunohistochemistry as an accessible adjunct in glioma diagnosis and clinicopathological stratification; outcome-based prognostic significance requires longitudinal follow-up.

Notably, the oncogenic idh1*R132H variant also rescued the pronephric defects induced by idh1 knockdown, indicating that its neomorphic activity is absent under embryonic metabolic conditions. These findings identify Idh1 and Idh2 as key regulators of pronephric morphogenesis and reveal a developmental function of Idh1 that is distinct from its canonical catalytic role.

P1, N=166, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2027 --> Oct 2030

P1/2, N=57, Active, not recruiting, Northwestern University | Trial completion date: Nov 2025 --> Dec 2026 | Trial primary completion date: Nov 2025 --> Dec 2026

We characterized the distribution of IDH1 mutations in a large cohort of patients with ICC from China. The presence of IDH1 mutations was associated with better survival and decreased risk of recurrence in patients with resected ICC that received adjuvant chemotherapy.

P1, N=30, Recruiting, Servier Bio-Innovation LLC

P2, N=50, Not yet recruiting, PETHEMA Foundation

We investigated the effects of short-term (5 days) and long-term (≥5 weeks) exposure to the IDH1 inhibitor AGI-5198 on radiation-induced cytotoxicity...Effects were comparable to short-term treatment, while radiation responses varied by genetic context. No deleterious interaction between IDHi and IR was observed in endogenous IDH-mutant cells except for MGG18 Tet+ supporting integration of IDHi with radiotherapy in IDH mutant gliomas.

IDH2 and TP53 mutations are enriched in dedifferentiated CS and are significant, independent predictors of adverse survival, regardless of tumor grade. These findings support IDH2 mutation status as clinically meaningful prognostic biomarker that may allow risk stratification and clinical decision-making in CS patients.

While no significant synergistic effects were observed in survival endpoints, differences emerged at the level of early DNA damage effects, with IDH1-mutant glioma cells displaying an enhanced acute response following combined treatment with proton irradiation. These findings support further pharmacological development of boron-based SRC-targeted strategies and underscore the importance of tailoring therapeutic approaches to specific glioma molecular subtypes.

The recurrent coexistence of IDH1 mutations with MAPK pathway and TERT promoter alterations supports a potential cooperative role within melanoma oncogenesis. These findings are descriptive and hypothesis-generating, and further studies with larger cohorts are required to clarify the biological and clinical relevance of IDH1 mutations in melanoma.