Lecture 8 - Cancer

Question 1

Cancer

Answer 1

• Selection should favor cells that can outreproduce other cells
  
  • Impetus for cancer
• Cells that differentiate lose the ability to proliferate
  
  • Creates a trade-off between specialization and proliferation
• Found in all multi-cellular organisms

Question 2

Cancer Prevention in Organisms

(TAC)

Answer 2

• Undifferentiated cells have ability to clone
• Differentiated cells do not reproduce
  
  • Transient amplifying cells: partially differentiated that increase proliferation of stem cells
  • Each TAC stage doubles descendant cells
• Metabolically expensive
  *

Question 3

Mathmatical simulations for TAC

Answer 3

• Stem cells exactly replicate themselves
  
  • But how low proliferation potential
• TAC do not replicate but high proliferation
• Self-renewal/proliferation required for selection
  
  • DNA must replicate itself and anything that promotes reproduction should be favored
• Implication: What if there are differentiated cells capable of proliferation?

Question 4

Insulin cells of pancreas

Answer 4

• Pancreatic islet cells are differentiated and capable of replication
  
  • Pancreatic cancer is very rare
  • Cells at risk of cancer development and cells at risk may be seen as cancerous
• Potential mechanism: Because they replicate, immune system may view this organ as suseptible to cancer
  
  • Maybe this explains Type 1 Diabetes?
  • When growth is rapid, immune system kills islet cells
• Immune system may be more susceptible to cancerous cells during reproductive years, thus low risk of pancreatic cancer during this time.
  *

Question 5

Type 1 Diabetes

and Type 2

Answer 5

• Type 1 usually in juveniles and especially those with type 1
• Relative of T2 risk highest when diabetes duration lower
  
  • In cases where diabetes has a long duration, risk of cancer is lower so therefore T2 likely not caused by cancer.
• If pancreatic cancer has a relationship to T2, its a negative association
  
  • Since pancreatic cancer is pretty lethal, not likely to have a long duration of T2
• Unclear if T2 causes cancer or cancer causes T2

Question 6

Warburgh Effect

(And math)

Answer 6

• Aerobic glycolysis produces ATP faster
  
  • Cancer uses this
  • Therefore, if we deprive cells of oxygen, more likely to become cancerous
• Fermentation (non-aerobic) outcompetes when lots of glucose is available
  
  • Fermentation population decreases over time though
  • Because it’s faster, but less efficient (makes less atp/glucose)

Question 7

Oxygen and Cancer

(and strategic usefulness of oxygen for cancer)

Answer 7

• Cancer cells can grow without oxygen
• Some types of cancer cells need oxygen though and have reduced ability to produce ATP from glycolysis (fermentation)
• Glycolysis can support higher growth rates for cancer cells
  
  • Does not produce oxygen radical so oxidative stress not a part of this and the cell won’t be damaged by it.
  • Because it doesn’t, an important trigger for cell death (apotosis) doesn’t occur so these cells can keep surviving
    *

Question 8

Poff et al (2013) - Experiment

Answer 8

• Restrict access of cancer cells to glucose
  
  • Give protein or fat
• Artificially increase levels of oxygen
  
  • To increase oxidative stress and help body target cells for destruction
• Control was given a standard diet, condition groups given low carb (kerotogen) diet, low carb with more oxygen, standard diet with oxygen
  
  • Standard diet + oxygen rats died sooner
• Low carb high oxygen and low carb survived the longest
• Kerotgen diet also significantly reduced weight
  
  • Lots of evidence suggests that underfeeding reduces cancer development

Question 9

Cachexia

(plus hypothesis)

Answer 9

• Loss of appetite, weight/muscle
• POSITIVE risk factor for death in cancer
  
  • Viewed as a negative symptom

1. Pathological symptom of cancer
   
   • Loss of body tissue fuels the cancer
   • But why loss of appetite?
     
     • Body trying to take control of the cancer by reducing energy intake
     • Adaptive response to cancer