Outline of Disease Process CANCER

Question 1

What does “cancers are mostly monoclonal” mean?

Answer 1

They mainly arise from one cell

Question 2

Whats different about cancer cells?

Answer 2

Increased growth factor secretion
Increased in oncogene expression
Loss of tumour supressor genes
Loss of contact inhibition

Question 3

What are the 5 steps of carcinogenesis?

Answer 3

Carcinogen
Initiation
Promotion
Tumour Growth
Progression

Question 4

What is a diagnostic threshhold?

Answer 4

The size at which a cancer becomes clinically detectable

Question 5

What are the 3 types of carcinogens?

Answer 5

Chemical
Physical
Viral

Question 6

What chemical carcinogen causes liver cancer?

Answer 6

Aflatoxin (in mouldy peanuts)

Question 7

Most common chemical carcinogens?

Answer 7

Smoking & alcohol

Question 8

Physical carcinogen?

Answer 8

Ionising radiation

Question 9

How does ionising radiation cause cancer?

Answer 9

Ionising radiation:
- Translocate chromosomes
- Amplify certain Genes
- Activate Oncogenes

Question 10

What viral carcinogen causes burkitts lymphoma?

Answer 10

Herpes virus causes burkitts lymphoma

Question 11

What viral carcinogen caues liver cancer?

Answer 11

HEP B can cause liver cancer.

Question 12

What 3 things are involved in the promotion stage?

Answer 12

Oncogens
Tumour supresser genes
Growth factors

Question 13

How do oncogenes promote the progression stage?

Answer 13

Oncogenes are positive regulaters of growth, they stimulate tumour growth

Question 14

How do growth factors stimulate cell growth?

Answer 14

Bind to cell-membrane receptors & activate intracellular signal transduction pathways

Question 15

Define autocrine signaling?

Answer 15

When a cell secretes a substance (i.e. growth factor) that acts on receptors on the same cell inducin changes in it

Question 16

Whats the difference between autocrine & paracrine signalling?

Answer 16

Paracrine signalling involves signals acting on nearby cells, autocrine involves signals acting on the same cell that produces them

Question 17

Whats the normal function of tumor suppressor genes?

Answer 17

Promoting DNA repair, Apoptosis & differentiation

Question 18

What normally induces tumor suppressor genes to act?

Answer 18

Hypoxia & DNA damage

Question 19

Name a tumor supressor gene

Answer 19

P53

Question 20

How does progression (metastasis) occur?

Answer 20

Tumour invades through basement membrane.
Invades into ECM/connective tissue/other cells
Invades blood vessles
Finally cells arressted in a distant tissue

Question 21

IS the progression stage random?

Answer 21

No its a series of limited sequential steps involivng host-tumor interactions

Question 22

At what point is angiogenesis vital for continued tumor growth?

Answer 22

New vessels must form for a tumour to grow beyond 2mm in diameter

Question 23

How does angiogenesis affect the ECM?

Answer 23

Enzymes degrade the ECM to allow for new vessel growth

Question 24

How is angiogenesis related to cancer severity?

Answer 24

Theres a correlation between vessel density and tumour malignancy/metastasis.

Question 25

How is angiogenesis inhibited?

Answer 25

-> Avastin (anti-VEGF antibody) binds to VEGF
-> prevents VEGF-receptor interaction

Question 26

What is the ultimate effect of anti-VEGF treatments?

Answer 26

Vascular regression & dormant tumours

Question 27

What is the purpose of T cell inhibition receptors?

Answer 27

TO maintain self-tolerance & protect tissue duing immune responses

Question 28

How do tumours blind T cells to them?

Answer 28

They express a specific ligand and bind to T cell inhibition receptors

Question 29

What ligand/receptor combo is used by cancers to blind T cells?

Answer 29

ligand on cancer cell = PDL-1
Receptor on T cell = PD1

Question 30

Explain therapeutic options to bypass T cell blindness to cancer cells?

Answer 30

Block PDL-1 on cancer cell or PD1 on T cell.
Or use modified aritifical T cells (chimeric antigen receptors, CAR T cells)