Hallmarks of cancer

Question 1

What are the hallmarks of cancer?

Answer 1

Gain Oncogenes
Loss Tumor suppressors
Spread/Growth distant sites
Gain Telomerase
Gain blood supply
Loss apoptosis

Question 2

What is the warburg effect?

Answer 2

the rate of glucose uptake dramatically increases and lactate is produced, even in the presence of oxygen (aerobic conditions) and fully functioning mitochondria

Question 3

What does lactate do?

Answer 3

allows the pathways to form and cancer cells are reliant on lactate

Question 4

what do cancer cells do in warburg?

Answer 4

Proliferative tissue or tumors can switch to glycolytic pathway, even in the presence of oxygen

so the glucose –> pyruvate and 85% goes to lactate and 5% goes to make CO2

Question 5

what do regular differentiated tissues do instead of warburg effect?

Answer 5

they have two pathways

aerobic (presence of oxygen): glucose –> pyruvate + O2 –> CO2

anaerobic (absence of oxygen): glucose –> pyryvate –> lactate

Question 6

Why is it so hard to “cure” cancer

Answer 6

cells have pathways and if you give treatment to one area, then cancer will use another pathways and you have to use another treatment

Question 7

What is reverse warburg effect?

Answer 7

cancer cells cause changes in surrounding normal (stromal cells)

they use normal cells to produce the warburg effect and reprogram them to produce lactate

Question 8

What do cancer cells release to switch stromal cells to aerobic glycolysis (warburg effect)

Answer 8

ROS (reactive oxidative species)

thus stromal cells produce lactate and transports this to cancer cells to use as energy and building blocks

Question 9

List the 6 OG hallmarks of cancer and what they do

Answer 9

1. oncogenes: stuck accelerator (increase in RAS)
2. loss of tumor suppressor: cutting the breaks (loss of RB)
3. cellular immortality: endless tank of gas (increase telomerase)
4. decrease apoptosis: increase prolife, decrease the prodeath signals (loss of P53)
5. angiogenesis: new blood vessel growth
6. metastasis: spreads to distant sites (loss of E-cadherin)

Question 10

What does E-cadherin do?

Question 11

why does increase telomerase lead to cellular immortality?

Answer 11

telomeres are a repeated sequence at the ends of the chromosomes that protect the chromosome from damage

each replication leads to the telomerase getting shortened, thus when it reaches a certain level this creates a crisis for the cell and it does not replicate anymore, so this will limit the cell proliferation

cancer cells re-express the telomerase leading to unlimited cell divison

Question 12

what is apoptosis and what controls it?

Answer 12

death of the cells, if there is too much cell damage then it will trigger cell death, so cancer needs to eliminate apoptosis

P53 is what controls apoptosis, so the loss of it will decrease the ability for the cell to experience death

Question 13

how do cancer cells decrease apoptosis?

Answer 13

by the gain of anti-apoptotic proteins (BCl-2)
&
loss of pro-apoptotic proteins (BAX or P53)

Question 14

What are the 4 new hallmarks?

Answer 14

1. Deregulating cellular energetics
2. Avoiding immune destruction
3. tumor promoting inflammation
4. genome instability and mutation

Question 14

What is deregulating cellular energetics/reprogramming energy metabolism and what is an example of it?

Answer 14

as cancer cells behave differently than normal cells, they alter the cellular metabolic pathways to support their needs

example: the warburg effect

Question 15

what is avoiding immune destruction?

Answer 15

tumors that survive the body’s immune system have successfully evaded detection or limited the immunological response of the body

Question 16

what is tumor-promoting inflammation?

Answer 16

signaling between the tumor microenvironment works to utilize the body’s immune cells to support further proliferation and metastasis

this inflammation works by supplying biomolecules to the tumor microenvironment such as: growth factors, survival factors, pro-angiogenic factors and ECM modifiers that stimulate angiogenesis, invasion, and metastasis

Question 17

what is genome instability and mutation? example?

Answer 17

as cancer cells proliferate so quickly, they accumulate mutations more frequently than normal cells. this is caused by increased senstivity to muatgenic agents, and the accumulation of other mutations that alter the surveillance systems that the cells already have in place

example: loss of P53