Characterising the effect of metabolic perturbation on oncogenic signalling transduction
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Embargo End Date
2026-05-12
ICR Authors
Authors
Harbery, A
Document Type
Thesis or Dissertation
Date
2025-11-12
Date Accepted
Abstract
Metabolic rewiring, including increased glucose dependence known as the Warburg
effect, is a hallmark of cancer. This PhD thesis investigates how metabolic
perturbations, specifically glucose deprivation, influence oncogenic signalling and the
initial response to inhibitors of oncogenic drivers, which remain underexplored. In EGFR
and BRAF-driven glioblastoma models, glucose deprivation causes super-activation of
driver oncogenes, leading to cell death—a process mitigated by selective tyrosine
kinase inhibitors. This suggests that glucose deprivation induces cell death through
oncogene overdose, irrespective of the oncogene type. Similar effects are observed in
other oncogene-driven models, hinting at broader applicability in oncogene-dependent
cancers. Molecular profiling reveals that glucose deprivation induces notable
transcriptional and phosphorylation changes, many reversible by oncogene inhibition.
Our findings indicate that glucose depletion triggers a non-apoptotic, possibly necrotic,
form of cell death linked to disrupted cell cycle checkpoint control. These insights
advance our understanding of the Warburg effect and inform strategies for combining
targeted therapies in cancer treatment.
Citation
2025
DOI
Source Title
Publisher
Institute of Cancer Research (University Of London)
ISSN
eISSN
Collections
Research Team
Molecular Addictions