12 cancer metabolism Flashcards
What is the definition of metabolism?
The chemical processes that occur within a living organism to maintain life.
How does metabolism reflect cell phenotype?
: It provides insight into cellular function, energy use, and biosynthetic activity.
Why do cancer cells have increased metabolic demands?
: They require more energy (ATP), biosynthetics (macromolecules), and redox buffering to support uncontrolled growth.
What are the stages of tumour development and progression?
Hyperplasia → Adenoma → Adenocarcinoma.
What did Freund discover in 1887 about cancer metabolism?
Blood cancers can be killed by glucose deprivation.
What was Müller’s contribution to cancer metabolism in 1890?
He observed changes in the metabolic composition of cancer patient urine.
What did Warburg propose about cancer metabolism in 1926?
Cancer cells exhibit increased glycolysis even in the presence of oxygen.
Who is considered the “Godfather of Cancer Glycolysis”?
Otto Warburg.
What is the Warburg Hypothesis?
Cancer cells have damaged respiration and ferment glucose excessively.
What is the Warburg Effect?
Cancer cells rely on glycolysis even in the presence of oxygen, leading to increased lactate production.
How does ATP production differ between normal and cancer cells?
Normal cells: 34 ATP via OxPhos + 2 ATP via glycolysis.
Cancer cells: 2 ATP via glycolysis with increased glucose flux.
What imaging technique is used based on Warburg’s principles?
18F-fluorodeoxyglucose PET/CT.
Why does FDG-PET work for cancer detection?
Cancer cells take up more glucose, and FDG accumulates without being metabolised.
How does Ras activation affect cancer metabolism?
It upregulates glucose uptake and glycolysis via PI3K/Akt signalling.
What happens when the VHL gene is lost in kidney cancer?
HIF signalling is activated, leading to widespread metabolic remodelling.
What is the function of the Pentose Phosphate Pathway in cancer?
Produces NADPH and ribose-5-phosphate for nucleotide biosynthesis.
How does glutamine metabolism support cancer cell growth?
Provides glutamate and α-ketoglutarate to fuel the TCA cycle.
What is the Hexosamine Pathway used for?
Produces UDP-GlcNAc for protein modification.
What is the structure of mitochondrial DNA?
A covalently-closed circular molecule located in the mitochondrial matrix.
How many protein-coding genes are in mtDNA?
13, all involved in oxidative phosphorylation (OXPHOS).
How do mtDNA mutations affect colorectal cancer?
They are enriched during adenoma-to-carcinoma progression and impact OXPHOS function.
How can mtDNA mutations alter cancer metabolism?
They upregulate serine synthesis, one-carbon metabolism, and amino acid transporter expression.
What is a key method to study cancer metabolomics?
Nuclear Magnetic Resonance (NMR) Spectroscopy.
What is Mass Spectrometry (MS) used for in cancer metabolism?
Detects metabolites based on their mass-to-charge ratio.
Q: How is metabolic pathway mapping performed in vivo?
Using radiolabelled isotopes like 13C-labelled glucose or glutamine.
Q: Are tumours composed only of cancer cells?
A: No, they also contain fibroblasts, immune cells, and extracellular matrix.
What is a key metabolic influence in the tumour microenvironment?
Nutrient availability and oxygen gradients.
How does nutrient deprivation affect tumour metabolism?
It induces catabolic “starvation responses” to maintain survival.
What happens to cells near blood vessels in a tumour?
They engage in anabolic metabolism to synthesise macromolecules.
How does hypoxia affect tumour metabolism?
It triggers metabolic changes via hypoxia-responsive transcription factors.
Name three transcription factors involved in hypoxia response.
HIF1, p53, and Myc.
How do cancer-associated fibroblasts contribute to tumour metabolism?
They use lactate from cancer cells for energy, supporting tumour growth.
How does metabolic reprogramming contribute to drug resistance?
It enables cancer cells to survive chemotherapy, radiotherapy, and targeted therapies.
Why is targeting cancer metabolism a promising strategy?
It bypasses redundancy in genetic mutations and impacts all cancer hallmarks.
Are anti-metabolic cancer therapies already in use?
Yes, some are already used for other diseases and could improve cancer treatment.
What major metabolic pathways are altered in cancer cells?
Glycolysis, pentose phosphate pathway, serine synthesis, and glutamine metabolism.
How can metabolism be studied at a snapshot level?
Using NMR Spectroscopy and Mass Spectrometry.
How does metabolic tracing differ from metabolomics?
It tracks real-time metabolic flux using radiolabelled isotopes.
What are the main cell-extrinsic factors influencing cancer metabolism?
Nutrient gradients, oxygen levels, and tumour microenvironment interactions.
Why is cancer metabolism a crucial area of research?
It provides insights into tumour growth, drug resistance, and potential therapies.
What experimental method allows live imaging of cancer metabolism?
FDG-PET imaging.
What role does the tumour microenvironment play in metabolic adaptation?
It influences metabolic phenotypes through factors like oxygen and nutrient levels.
What is the role of serine synthesis in cancer?
Supports nucleotide biosynthesis and antioxidant production.
What metabolic pathway produces ribose-5-phosphate?
he Pentose Phosphate Pathway.
How do cancer cells maintain ATP production when OxPhos is damaged?
They rely on increased glycolysis.
What are two common metabolic alterations in colorectal cancer?
Increased glucose uptake and OXPHOS defects.
Why is lactate production high in cancer cells?
Due to the Warburg Effect, where glycolysis is used even in oxygen-rich conditions.
