OPTIMIZATION OF DEMETHYLATING THERAPY FOR IDH1 MUTANT GLIOMAS

Mutant IDH1 regulates the tumor-associated immune system in gliomas.

Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In orde...

PLK1 inhibition enhances temozolomide efficacy in IDH1 mutant gliomas

Despite multimodal therapy with radiation and the DNA alkylating agent temozolomide (TMZ), malignant gliomas remain incurable. Up to 90% of grades II-III gliomas contain a single mutant isocitrate dehydrogenase 1 (IDH1) allele. IDH1 mutant-mediated transformation is associated with TMZ resistance; however, there is no clinically available means of sensitizing IDH1 mutant tumors to TMZ. In this ...

Metabolism, gliomas, and IDH1.

Mutant IDH1 is required for IDH1 mutated tumor cell growth

Frequent somatic hotspot mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, acute myeloid leukemias, chondrosarcomas, and other cancers, providing a likely avenue for targeted cancer therapy. However, whether mutant IDH1 protein is required for maintaining IDH1 mutated tumor cell growth remains unknown. Here, using a genetically engineered inducible system, we repor...

Expression of IDH1 Mutant Protein R132H and SDHB in Adult and Pediatric Gliomas

Isocitrate dehydrogenase 1 (IDH1) and Succinate dehydrogenase (SDH) mutant tumors may have increased levels of hypoxia inducible factor (HIF), which leads to a tumoral pseudohypoxic profile. Increased HIF levels may promote tumor progression by the activation of numerous cellular processes including resistance to apoptosis, vascular remodeling and angiogenesis. A high frequency of IDH1 mutation...