Anticancer agents

Question 1

function of KRAS

Answer 1

transmits external growth signals to the nucleus
drives cell growth

Question 2

how is KRAS activated/inactivated

Answer 2

activated - binding to GTP
inactivated - when the bound GTP is hydrolysed to GDP

Question 3

what is the function of Glivec (imitanib)

Answer 3

holds the activation loop in an inactive state , preventing dimerisation
preventing cell survival
acts as a tyrosine kinase inhibitor

Question 4

how do cancer cells resist glivec

Answer 4

mutant in the ABL locus
threonine to isoleucine

Question 5

what percentage of patients will need alternative treatment due to imitanib therapy

Answer 5

20-40%

Question 6

what drug overcomes imitanib resistance and how

Answer 6

Dasatinib, sprycel
binds to active form of ABL
overcomes 14 of the 15 imitanib mutations

Question 7

what percentage of patients unresponsive to imitanib responded to nilotinib

Answer 7

92%

Question 8

what mutation can nilotinib (a second generation) not target

Answer 8

T315I

Question 9

what is a third generation bcr-abl inhibitor

Answer 9

SGX393

Question 10

what would be the point of combination therapy of nilotinib/dasatinib (second generation with) with SGX393

Answer 10

to pre-empt any bcr-abl inhibitor resistant mutations

Question 11

what is the most common mutation cancer cells employ to resistant EGRF inhibiting antibodies

Answer 11

T790M

Question 12

how do second generations EGFR TKI’s perform their function

Answer 12

form irreversible covalent bonds with the ATP-binding site of EGFR as well as other HER family of receptors

Question 13

what mutation can only 3rd generation EGFR TKI’s target

Answer 13

T790M

Question 14

how does vemurafenib inhibit cutaneous melanomas

Answer 14

40-60% of cutaneous melanomas are positive for a BRAF mutation - BRAF V600E compromise 90% of those mutations
vemurafenib blocks BRAF V600E
blocking the survival signals to the cell

Question 15

what are the different ways cancer cells can reestablish their survival signals

Answer 15

increase in COT - to activate MEK
direct MEK1/2 mutations - to activate ERK
other BRAF V600E mutation

Question 16

what do tumour cells express to prevent an immune response

Answer 16

PD-1 receptors

Question 17

what is the outcome of using anti-PD-1 antibodies

Answer 17

T-cells able to elicit anti-tumour response

Question 18

function of Bevacizumab (avastin)

Answer 18

targets vascular endothelial growth factor (VEGF)
creates hypoxic conditions surrounding the tumour

Question 19

what does chemotherapy target

Answer 19

targets all fast-growing cells

Question 20

what is the function of alkylating agents as a chemotherapeutic

Answer 20

cross-links two DNA strands to prevent DNA replication

Question 21

function of cisplatin

Answer 21

also cross-links DNA

Question 22

function of antimetabolites as chemotherapeutics

Answer 22

produce analogous that compete with DNA synthesis
methotrexate - folic acid analogue
5-FU - thymine analogue
cytarabine - pyrimidine analogue

Question 23

function of plant alkaloids and their mechanism of action

Answer 23

they are mitotic inhibitors
bind to tubulin - interferes with spindle assembly in mitosis

Question 24

what is the function of the second class of plant alkaloids

Answer 24

topoisomerase inhibitors - inhibits the unwinding of supercoiled DNA

Question 25

what is the function of antibiotics in terms of chemotherapy

Answer 25

binds non-covalently to DNA
cell cycle stage - non-specific