Hallmarks of Cancer

Question 1

Name 5 methods cancer cells can sustain proliferative signalling.

Answer 1

• producing GF ligands themselves to which they can respond via receptors, resulting in autocrine proliferative stimulation
• sending signals to stimulate normal cells to produce GFs resulting in paracrine proliferative stimulation
• increasing the expression or change the structure of receptor proteins on the surface, rendering themselves hyper-responsive to GFs
• activating components of signalling pathway downstream from receptors, obviating the need to stimulate these receptors with GF ligand
• disrupting negative feedback mechanisms that attenuate proliferative signalling

Question 2

What does the c-myc gene encode?

Answer 2

pro-growth Myc protein

Question 3

What do Myc-Max dimers favour?

Answer 3

growth and proliferation

Question 4

What are telomeres composed of?

Answer 4

multiple tandem hexanucleotide repeats

Question 5

What is the function of telomeres?

Answer 5

protect the ends of chromosomes and are involved in the capability of unlimited proliferation

Question 6

What happens to telomeres over time?

Answer 6

they shorten progressively in normal cells, eventually losing the ability to protect the ends of chromosomal DNA from end-to-end fusions

Question 7

What is telomerase?

Answer 7

an specialised DNA polymerase that adds telomere repeat segments to the ends of telomeric DNA

Question 8

How is telomerase exploited in cancer?

Answer 8

telomerase is almost absent in normal cells; however in cancer a vast majority of cells have telomerase expressed at a functionally significant level, making the cancer cells immortalised

Question 9

What is angiogenesis?

Answer 9

the development of new blood vessels from pre-exisiting vessels

Question 10

Which molecule promotes angiogenesis?

Answer 10

VEGF

Question 11

Which molecule is anti-angiogenic?

Answer 11

Thrombospondin

Question 12

Which molecule is anti-angiogenic?

Answer 12

Thrombospondin

Question 13

What drugs are used to target “sustaining proliferative signalling”?

Answer 13

EGFR inhibitors

Question 14

What drugs are used to target “evading growth suppressors”?

Answer 14

CDK inhibitors

Question 15

What drugs are used to target “avoiding immune destruction”?

Answer 15

Immune activating anti-CTLA4 mAb

Question 16

What drugs are used to target “enabling replicative mortality”?

Answer 16

Telomerase inhibitors

Question 17

What drugs are used to target “deregulating cellular energetics”?

Answer 17

Aerobic glycolysis inhibitors

Question 18

What drugs are used to target “resisting cell death”?

Answer 18

Pro-apoptotic BH3 mimetics

Question 19

What drugs are used to target “genome instability & mutation”?

Answer 19

PARP inhibitors

Question 20

What drugs are used to target “inducing angiogenesis”?

Answer 20

Inhibitors of VEGF signalling

Question 21

What drugs are used to target “Activating invasion and metastasis”?

Answer 21

HGF/c-Met inhibitors

Question 22

What drugs are used to target “tumour promoting inflammation”?

Answer 22

Selective anti-inflammatory drugs

Question 23

Define the hallmarks of cancer.

Answer 23

Genome instability & mutation
Resisting cell death
Evading growth suppressors 
Avoiding immune destruction
Tumour promoting inflammation

Inducing angiogenesis 
Deregulating cellular energetics
Enabling replicative mortality
Activating invasion & metastasis 
Sustained proliferative signalling

Question 24

Discuss the changes in cadherin molecules associated with cancer

Answer 24

E-cadherin is down-regulated frequently in human carcinomas

N-cadherin is often up-regulated

Question 25

What is E-cadherin?

Answer 25

a key cell-to-cell adhesion molecule

Question 26

What is N-cadherin?

Answer 26

an adhesion molecule normally associated with cell migration during embryogenesis and inflammation