Cancer- Hallmarks

Question 1

When were cancer genomes first provided?

Answer 1

Glioblastomma genome 2008, was used to see all the mutations in a tumour
Showed that the vast majority of human tumours show malfunctions in the same functional networks

Question 2

What’s another cancer genome example?

Answer 2

Prostate cancer genome- 2010
All common tumour types have now been studied extensively to identify mutations

Question 3

How are mutations in tumours split?

Answer 3

‘Driver mutations’ which actively drive the cancer
AND
‘Passenger mutations’ which are more common but do not drive hallmarks of cancer

Question 4

Is tumourigenesis a multi-step process?

Answer 4

Yes
These steps involve a succession of genetic changes which drive progressive transformation of normal cells to malignant derivatives

Question 5

For most cancers, what 10 acquired capabilities underpin malignant cell growth?

Answer 5

• Self-sufficiency in growth signals
• Insensitivity to growth inhibitory signals
• Evasion of apoptopsis
• Limitless replicative potential
• Sustained blood supply
• Tissue evasion and metastasis
• Deregulated cellular energetics
• Avoiding immune destruction
• Genome instability
• Tumour promoting inflammation

Question 6

In normal cells, how do growth signals work?

Answer 6

Normal cells only move from G0 into active proliferation in response to mitogenic growth signals received from surrounding cells

Question 7

How does self-sufficiency in growth signals work in cancer cells?

Answer 7

Most cancer cells have mutations in at least one component if this growth control system which drives cell proliferation

Question 8

What is the usual signalling process for growth factors?

Answer 8

Growth signals- transmitted into the cell by transmembrane receptors
These then trigger multiple signal transduction pathways
Eventually reaching nucleus where it instructs synthesis of proteins and enzymes for cell growth

Question 9

What is wrong with the signalling process in cancer?

Answer 9

Many cancers have defects in signalling processes
Many tumour cells have the ability to generate their own growth signals

Question 10

What does aberrant over-activation of growth factor signalling in cancer cells mean?

Answer 10

Means that cancer cell proliferation is less dependent on activation by surrounding cells
Tumour cells achieve this in 3 ways

Question 11

How do cancer cells synthesize their own growth factors?

Answer 11

Can attract other normal cells into a tumour which synthesize growth factors
Transmembrane receptors become deregulated
Cancer cells can develop alterations in components of the downstream cytoplasmic circuitry

Question 12

Within normal cells, what suppresses growth?

Answer 12

Many growth inhibitory signals operate to maintain cellular quiescence and tissue homeostasis
Signals include:
- Soluble growth inhibitors
- Immobilised inhibitors

Question 13

What is the usual way a cell will stop proliferating?

Answer 13

Most cells, will stop proliferating when they are surrounded by neighbouring cells. Instruction to stop dividing is active

Question 14

Why is apoptopsis important in normal cells?

Answer 14

Prevents proliferation of abnormal or faulty cells
Apoptopsis is important in destroying cells that escape from their normal tissue environment or position

Question 15

How do cancer cells evade apoptopsis?

Answer 15

The most common strategy involves mutation of the p53 tumour supressor gene
Healthy p53 drives apoptopsis in damaged cells
Cancers lack this due to mutation in p53

Question 16

What replicative potential do normal cells have?

Answer 16

Finite
After 40-60 doublings they stop counting device

Question 17

What is senescence?

Answer 17

A permanent growth arrest enforced by systems including p53 in response to different stresses, including short telomeres

Question 18

What is a telomere?

Answer 18

Is a polynucleotide region at the end of linear chromosomal DNA
Germ cells (and many cancer cells) express telomerase, an enzyme which makes telomeres

Question 19

What do telomeres play a role in?

Answer 19

In protecting ends of chromosomal DNA
However, with each replication, length of telomere shortens 50-100 base pairs
This is because DNA polymerase cannot replicate the 3 end of the lagging strand

Question 20

What does telomere shortening trigger?

Answer 20

A DNA damaging signal resulting in growth arrest and these cells enter senescence

Question 21

How do cancer cells achieve an immortal cell phenotype?

Answer 21

Telomerase, an RNA dependent DNA polymerase has the ability to add hexanucleotide repeats onto the ends of telomeric DNA and thus maintain telomere length

Question 22

How common is telomere maintenance in cancer cells?

Answer 22

Is evident in virtually all types of malignant cells
85-90% of these do so by up regulating expression telomerase

Question 23

Why is angiogenesis important?

Answer 23

Oxygen and nutrients supplied by blood vessels crucial for cell survival

Question 24

How do tumour cells sustain angiogenesis?

Answer 24

As a tumour grows in size, it’s central cells become remote from blood supply, starved of oxygen and nutrients
Tumour cells express pro angiogenic factors

Question 25

Where are the most common cancers derived from?

Answer 25

(lung, breast, prostate, colon)
Are derived from tissues that form sheets of joined cells, known as epithelia
Called ‘carcinomas’

Question 26

What are cadherins and E-cadherins?

Answer 26

Cadherins are ubiquitous calcium dependent cell-cell adhesion molecules
E-cadherins is required for normal adhesion in epithelial tissues