4- cancer cell metabolism Flashcards
Why is targeting cancer cell metabolism an attractive approach for cancer treatment?
Targeting cancer cell metabolism is attractive because cancer cells exhibit unique metabolic characteristics, such as increased uptake of nutrients like glucose and glutamine. Drugs targeting these features have the potential to treat various cancers while sparing normal cells.
What is the Warburg effect, and why is it significant in cancer metabolism?
The Warburg effect, discovered by Otto Warburg, describes how cancer cells metabolize glucose into lactate even in the presence of oxygen (aerobic glycolysis). Despite being less efficient, this process is a hallmark of cancer cells, providing building blocks for rapid proliferation.
How do cancer cells shift from catabolic to anabolic metabolism, and why is this shift important?
Cancer cells shift from catabolic to anabolic metabolism to support increased protein, nucleic acid, and lipid synthesis for rapid proliferation. This shift involves altered nutrient uptake, including amino acids like glutamine, essential for nucleotide and amino acid synthesis.
Why do cancer cells exhibit the Warburg effect, and what are some theories about the underlying reasons?
The exact reasons for the Warburg effect in cancer cells are not fully understood. While Otto Warburg initially suggested mitochondrial injury, recent evidence contradicts this. Proliferating cells may prefer aerobic glycolysis for efficient metabolic pathway utilization.
How does the loss of FH (fumarate hydratase) influence cellular metabolism, and what compensatory mechanisms do FH-deficient cells employ?
Loss of FH leads to TCA cycle truncation and fumarate accumulation, reducing mitochondrial respiration. FH-deficient cells compensate by shifting to aerobic glycolysis, diverting glucose to the pentose phosphate pathway and increasing glutamine oxidation.
What are some key steps in cancer metabolism, particularly downstream of receptor tyrosine kinase signaling?
Key steps include increased growth factor signaling through the PI3 kinase pathway, resulting in elevated glucose uptake, upregulation of glycolysis genes, shunting of glucose into the pentose phosphate pathway, increased protein and amino acid uptake, and export of citrate for fatty acid synthesis.
Why do cancer cells undergo aerobic glycolysis, and how is it different from normal cell glucose metabolism?
Cancer cells undergo aerobic glycolysis (Warburg effect) to produce building blocks for proliferation. Unlike normal cells that primarily oxidize glucose in mitochondria, cancer cells convert a significant portion to lactate, even in the presence of oxygen.
How do mutations in oncogenes, such as those in the PI3K-AKT-mTOR network, influence tumor metabolism?
Mutations in oncogenes like PI3K-AKT-mTOR lead to high signaling levels, promoting anabolic programs involving increased glycolytic flux and fatty acid synthesis. These mutations alleviate the need for direct mutations in metabolic enzymes.
How does inhibition of the Electron Transport Chain (ETC) affect cancer cell proliferation, and why can pyruvate rescue this inhibition?
Inhibition of the ETC suppresses cancer cell proliferation. Pyruvate can rescue this inhibition by converting into lactate, using excess NADH generated by ETC blockage, thereby reducing NADH accumulation.
