Title:A Promising Breakthrough: The Potential of VORASIDENIB in the Treatment
of Low-grade Glioma
Volume: 17
Author(s): Alice Bombino*, Marcello Magnani and Alfredo Conti
Affiliation:
- Neurosurgery, IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy, Dipartimento di Scienze Biomediche e NeuroMotorie (DIBINEM), Alma
Mater Studiorum University of Bologna, Bologna, Italy
Keywords:
Vorasidenib, Low-grade gliomas, Brain tumors, Idh, Inhibitors, Future challenges.
Abstract:
Background:
This commentary explores the potential of Vorasidenib, also known as AG-881. This emerging small-molecule inhibitor has garnered substantial
attention within the realm of oncology due to its unique mechanism of action and potential therapeutic applications.
Introduction:
Gliomas are common malignant brain tumors characterized by diffuse brain infiltration. World Health Organization grade II and grade III diffuse
gliomas are considered lower-grade gliomas (LGGs) and have isocitrate dehydrogenase (IDH) mutations. LGGs are challenging due to their
infiltrative nature, making them capable of progressing into higher-grade malignancies. Vorasidenib is a novel therapeutic agent targeting mutant
IDH1/2, sparking interest in the field.
Mechanism of Action:
Vorasidenib inhibits mutant IDH1/2 through a unique mechanism, reducing the production of the oncometabolite 2-hydroxyglutarate (2-HG). This
alteration affects key enzymes and DNA methylation, impacting tumor growth and invasion.
Preclinical Evidence:
Preclinical studies show vorasidenib's efficacy in inhibiting mutant IDH1/2 and 2-HG production in glioma models. It suppresses tumor growth,
making it a potential treatment option.
Clinical Evidence:
Early clinical trials demonstrate vorasidenib's clinical activity in non-enhancing gliomas. It reduces 2-hydroxyglutarate levels and tumor cell
proliferation, with an objective response rate and prolonged progression-free survival. The drug's safety profile is favorable.
Challenges and Future Directions:
Challenges include identifying predictive biomarkers and optimizing sequencing or combinations with existing therapies. Further research is
needed to establish long-term effectiveness, evaluate side effects, and explore combinations with immunotherapy.
Conclusion:
Vorasidenib significantly advances LGG treatment, targeting a prevalent mutation and slowing tumor growth. Promising preclinical and clinical
evidence and manageable side effects suggest its potential impact on LGG management. However, more research, including large trials, is needed
to confirm its efficacy and role in treatment.
