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Activity Number:
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197
- SPAAC Poster Competition
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Type:
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Topic Contributed
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Date/Time:
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Monday, August 8, 2022 : 2:00 PM to 3:50 PM
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Sponsor:
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Statistics and Pharmacometrics Interest Group
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Abstract #322712
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Title:
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The Impact of MEK-Inhibitors on Neurofibromatosis Type 1 Associated Metabolism
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Author(s):
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Sophie Lu* and Ali Rahnavard and Brendan Mann and Miriam Bornhorst
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Companies:
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George Washington University and George Washington University and George Washington University School of Medicine and Health Sciences and Childrens National Hospital
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Keywords:
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cancer;
metabolomics;
omics
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Abstract:
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Neurofibromatosis Type 1 (NF1) is an autosomal dominant neurocutaneous syndrome caused by genetic inactivation of one copy of the tumor suppressor gene NF1. Loss of NF1 results in increased activity of Raf/MEK/ERK (MAPK) signalling leading to an increased risk of cancer and metabolic dysfunction. MEK-inhibitors (MEKi) have recently been approved for the treatment of inoperable plexiform neurofibromas or low grade gliomas (LGG) in patients with NF1, but their impact on restoring metabolic homeostasis is unknown. Here, we specifically investigated the longitudinal effects of MEKi treatment on global metabolism using Nf1 murine models and compared to metabolomic data in human patients to confirm our findings. Differential analysis of metabolomic data was conducted using Tweedieverse to analyze individual metabolites. Omics pathway enrichment analysis to analyze pathway-level changes was performed using Deepath. Metabolites associated with glucose metabolism, long-chain fatty acid synthesis, and amino acid transport were detected and help us form new hypotheses on the mechanisms that allow MEKi treatments to reverse the effects of disease.
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Authors who are presenting talks have a * after their name.
