IDH1

IDH1 Full Name

isocitrate dehydrogenase 1 (NADP+), soluble

IDH1 Introduction

The presence of an IDH1 mutation, most commonly detected via DNA sequencing or immunohistochemistry for the R132H variant, has become a central diagnostic and prognostic biomarker in neuro-oncology. In gliomas, IDH1 mutation status is now a fundamental criterion for tumor classification . Patients with IDH1-mutant gliomas have a significantly more favorable prognosis and respond better to standard therapies (like temozolomide and radiotherapy) compared to those with IDH1-wildtype tumors, which are more aggressive. The mutation serves as an early clonal event, and its detection can aid in distinguishing primary glioblastoma (usually IDH1-wildtype) from secondary glioblastoma (usually IDH1-mutant). Furthermore, mutant IDH1 itself is a direct therapeutic target.

Figure 1. Strcuture of isocitrate dehydrogenase 1.

Diagnostic, Prognostic, and Predictive Value
The presence of an IDH1 mutation, most commonly detected via DNA sequencing or immunohistochemistry for the R132H variant, has become a central diagnostic and prognostic biomarker in neuro-oncology. In gliomas, IDH1 mutation status is now a fundamental criterion for tumor classification in the WHO system. Patients with IDH1-mutant gliomas have a significantly more favorable prognosis and respond better to standard therapies (like temozolomide and radiotherapy) compared to those with IDH1-wildtype tumors, which are more aggressive. The mutation serves as an early clonal event, and its detection can aid in distinguishing primary glioblastoma (usually IDH1-wildtype) from secondary glioblastoma (usually IDH1-mutant). Furthermore, mutant IDH1 itself is a direct therapeutic target.

Clinical Significance and Targeted Therapy
The discovery of mutant IDH1's role led to the development of targeted small-molecule inhibitors. These drugs, such as ivosidenib, are designed to selectively bind to the mutant enzyme's active site, potently inhibiting the production of the oncometabolite 2-HG. Ivosidenib is approved by the FDA for the treatment of relapsed/refractory AML with a susceptible IDH1 mutation and, more recently, for previously untreated IDH1-mutant AML in patients ineligible for intensive chemotherapy. In solid tumors, ivosidenib has also shown clinical activity in advanced IDH1-mutant cholangiocarcinoma. Clinical trials are ongoing to evaluate these inhibitors, both alone and in combination with other agents (e.g., chemotherapy, immunotherapy), in glioma and other cancers. This represents a paradigm shift towards metabolic precision therapy.

Alternate Names for IDH1

IDH1; isocitrate dehydrogenase 1 (NADP+), soluble; IDH; IDP; IDCD; IDPC; PICD; HEL-216; HEL-S-26; isocitrate dehydrogenase [NADP] cytoplasmic

• Immunohistochemistry Antibodies for Pathology