IDH2 Inhibitors Gain a Wildcard Status in the Cancer Therapeutics Competition

The metabolic reprogramming characteristic of cancer cells, including the Warburg effect, has long been recognized as a hallmark of malignancy. This commentary explores three recent investigations focusing on the role of wild-type IDH2 in cancer and immune cell function. The first publication identi...

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Bibliographic Details
Published in:Cancers 2024-09, Vol.16 (19), p.3280
Main Authors: Piva, Roberto, Gharari, Nariman, Labrador, Maria, Mader, Sylvie
Format: Article
Language:English
Subjects:
Apoptosis
Breast cancer
Cancer immunotherapy
Cancer therapies
CD8 antigen
Cell differentiation
Cell growth
Cell therapy
Clinical outcomes
Dehydrogenases
DNA repair
Energy metabolism
Enzymes
Fatty acids
Immunological memory
Immunotherapy
Leukemia
Lymphocytes
Lymphocytes T
Malignancy
Memory cells
Metabolism
Metabolites
Mutation
Proteins
Therapeutic targets
Tumors
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Summary:The metabolic reprogramming characteristic of cancer cells, including the Warburg effect, has long been recognized as a hallmark of malignancy. This commentary explores three recent investigations focusing on the role of wild-type IDH2 in cancer and immune cell function. The first publication identifies wild-type IDH2 as a crucial factor in the survival of triple-negative breast cancer (TNBC) cells, with its inhibition leading to disrupted energy metabolism, reduced tumor growth, and enhanced apoptosis. The second analysis examines the role of IDH2 in CD8+ T cells, revealing that its inhibition promotes the differentiation of memory T cells, thereby enhancing the efficacy of cell-based immunotherapies like CAR T cells. A third investigation supports these findings, demonstrating that IDH2 inhibition in CAR T cells reduces exhaustion, enhances memory T cell formation, and improves anti-tumor efficacy. Collectively, these reports highlight wild-type IDH2 as a promising therapeutic target, with potential applications as a two-edged sword in both cancer treatment and immunotherapy. The development of specific wild-type IDH2 inhibitors could offer new avenues for therapy, particularly in tumors reliant on IDH2 activity as well as in enhancing the effectiveness of CAR T cell therapies.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers16193280