Publications by authors named "Abigail R Molloy"
Although lower grade gliomas are driven by mutations in the isocitrate dehydrogenase 1 (IDH1) gene and are less aggressive than primary glioblastoma, they nonetheless generally recur. IDH1-mutant patients are increasingly being treated with temozolomide, but early detection of response remains a challenge and there is a need for complementary imaging methods to assess response to therapy prior to tumor shrinkage. The goal of this study was to determine the value of magnetic resonance spectroscopy (MRS)-based metabolic changes for detection of response to temozolomide in both genetically engineered and patient-derived mutant IDH1 models.
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- Mutations in the IDH1 gene are prevalent in low-grade gliomas and secondary glioblastomas, driving tumor growth through the conversion of α-ketoglutarate to the oncometabolite 2-hydroxyglutarate.
- Inhibitors like AG-120 and AG-881 show promise in treating these tumors, though measuring their effectiveness can be difficult without visible tumor growth changes.
- This study identified potential metabolic imaging biomarkers, specifically using H- and C-magnetic resonance spectroscopy, to track treatment responses by monitoring levels of 2-HG and glutamate in glioma cells.
70-90% of low-grade gliomas and secondary glioblastomas are characterized by mutations in isocitrate dehydrogenase 1 (IDHmut). IDHmut produces the oncometabolite 2-hydroxyglutarate (2HG), which drives tumorigenesis in these tumors. The phosphoinositide-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway represents an attractive therapeutic target for IDHmut gliomas, but noninvasive indicators of drug target modulation are lacking.
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