Carcinogenesis and hallmarks of cancer

Question 1

electrophiles

Answer 1

many carcinogens are strong electrophiles that accept electrons

Question 2

3 steps

Answer 2

initiation
promotion (reversible)
progression (irreversible)

Question 3

smoking

Answer 3

causes chronic inflammation, and repair, which will eventually lead to cancer

Question 4

radiation

Answer 4

ionising - very high energy. inc cosmic rays & X-rays

non-ionising - less energy. inc UV rays

Question 5

ionising radiation

Answer 5

damages cellular structures and DNA
displaces electrons from atoms resulting in an ion pair

bone marrow, thyroid and breast tissue are particularly susceptible

Question 6

radiation therapy

Answer 6

splitting the dose will diminish the acute toxicity of the dose
only 3x the radiation received from therapy is fatal

Question 7

non-ionisning

Answer 7

UV A/B/C

C is the most potent but most is absorbed in the air

Question 8

nucleotide excision repair pathway

Answer 8

repairs distortions caused by UV radiation

errors in this pathway increase the risk of UV radiation

Question 9

highest risk factors for cancer

Answer 9

1. diet
2. smoking
3. infections

Question 10

oncogenic mutation

Answer 10

single mutation
dominant gene
gain of function triggering the development of cancer

Question 11

tumour suppressor genes

Answer 11

recessive
therefore requires 2 mutations
involve loss of function to develop cancer

Question 12

multistep carcinogenesis

Answer 12

90% of all human cancers are not familial

not the consequence of known familial factors`

Question 13

cancer and tissue oxygenation

Answer 13

cancers are hypoxic, and grow in a low oxygen environment
O2 can only diffuse 150microns
therefore only a very small portion of the tumour will be oxygenated due to distance between cancer cells and blood vessels (also makes it difficult to deliver anti-cancer medications into tumour)
blood vessels supplying blood to tumours are also hypoxic

Question 14

tyrosine kinase

Answer 14

HER1/2/3/4
requires dimerisation
HER1+1 normal, less proliferation
HER1=2 heterodimer is more proliferative
if a mutation triggers more HER2, then more heterodimers form, and more proliferation

Question 15

combretastatin A4

Answer 15

cuts of blood supply to endothelium surrounding tumor, depriving the tumour of blood
does cause ischaemic tumour pain, but effective at reducing tumour cells, particularly when given after chemo, whereby it can ‘trap’ the chemo agents within the tumour

Question 16

necrosis

Answer 16

promotes angiogenesis due to recruitment of inflammatory immune cells
therefore in tumours, necrotic cell death actually promotes tumour growth
normal healthy process which promotes wound healing, but us subverted by cancer to heal damage to tumour

Question 17

autophagy

Answer 17

cellular constituents degraded by lysosomal machinery within the cell