Day 7, Lecture 4 (Aug 30): Cancer II: Carcinogenesis

Question 1

Carcinogenesis

Answer 1

The process by which cells acquire attributes that confer a malignant phenotype. This is a synonym for the [obsolete] term cancerogenesis”

Question 2

Question 3

Question 4

Question 5

Question 6

Explain how Malignancy is typically a stepwise process

Answer 6

Question 7

Do cancer’s invent new biological properties through which they achieve the malignant phenotype

Answer 7

They simply borrow exisiting cellular pathways

Question 8

Hallmarks of cancer?

Answer 8

Question 9

Describe Hallmark 1 (How cancers avoid apoptosis)

Answer 9

Question 10

Effect of increasing BCL2 in cancer cells

Answer 10

Question 11

Explain hallmark 2 of Cancer cells: cancer cells use growth signaling pathways

Answer 11

• example:
  
  • Breast carcinoma
    
    • oncogene: HER2, a receptor tyrosine kinase
      
      • Amplification (too many copies) of HER2 (aka ERBB2) → overexpression of HER2 → increased signaling → proliferation

Question 12

How can HER2 amplication (in breast carcinoma) be detected

Answer 12

• by FISH (fluoroescence in-situ hybridization)
  
  • Marks centromeres and HER2 gene
  • then you do counts

Question 13

Breast carcinoma with HER2 amplification respond to what drug

Answer 13

• Trastuzumab

Question 14

Explain Hallmark 3 of cancer cells: cancer cells escape control of growth

Answer 14

• example RB is the “master brake” protein at G₁ to S (tumor suppressor)
  
  • in some cancers Rb is mutated and not able to bind to E2F and stop it from pushing the cell cyle forward

Question 15

Question 16

Question 17

Answer 17

Question 18

What is bevacizumab used to treat

Answer 18

It is a VEGF (Vascular endothelial growth factor) inhibitor and thus turns of angiogenesis

Question 19

Explain Hallmark 5: cancer cells divide without end

Answer 19

• Telomeres normally shorten with age.
  
  • normal cells observe the Hayflick limit
    
    • this means they stop dividing (senescence) due to shortening of telomeres
• Normal cells have little to no telomerase activity while cancer cells have high telomerase, which rebuilds the telomeres after division. Thus they are immortalized

Question 20

Answer 20

Question 21

_____ loss and matrix _____ allow cancer invasion

Answer 21

E-cadherin and matrix metalloproteinases (which eat through basement membrane) allow invasion

Question 22

Do tumor cells communicate with normal cells

Answer 22

Yes

Question 23

local conditions that enable cancer growth, brought about by interactions of tumor cells with stroma, inflammatory cells, blood vessels, etc.

Answer 23

Tumor microenvironment

Question 24

what is the warburg effect

Answer 24

• (“aerobic glycolysis”)
• It is an emerging hallmark that cancer cells have altered metabolism

Question 25

Explain the emerging hallmark: cancer cells escape detection

Answer 25

• cancer cells can turn off antigen expression and secrete antipoliferative factors

Question 26

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Question 28