Anticancer agents Flashcards
function of KRAS
transmits external growth signals to the nucleus
drives cell growth
how is KRAS activated/inactivated
activated - binding to GTP
inactivated - when the bound GTP is hydrolysed to GDP
what is the function of Glivec (imitanib)
holds the activation loop in an inactive state , preventing dimerisation
preventing cell survival
acts as a tyrosine kinase inhibitor
how do cancer cells resist glivec
mutant in the ABL locus
threonine to isoleucine
what percentage of patients will need alternative treatment due to imitanib therapy
20-40%
what drug overcomes imitanib resistance and how
Dasatinib, sprycel
binds to active form of ABL
overcomes 14 of the 15 imitanib mutations
what percentage of patients unresponsive to imitanib responded to nilotinib
92%
what mutation can nilotinib (a second generation) not target
T315I
what is a third generation bcr-abl inhibitor
SGX393
what would be the point of combination therapy of nilotinib/dasatinib (second generation with) with SGX393
to pre-empt any bcr-abl inhibitor resistant mutations
what is the most common mutation cancer cells employ to resistant EGRF inhibiting antibodies
T790M
how do second generations EGFR TKI’s perform their function
form irreversible covalent bonds with the ATP-binding site of EGFR as well as other HER family of receptors
what mutation can only 3rd generation EGFR TKI’s target
T790M
how does vemurafenib inhibit cutaneous melanomas
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
what are the different ways cancer cells can reestablish their survival signals
increase in COT - to activate MEK
direct MEK1/2 mutations - to activate ERK
other BRAF V600E mutation
what do tumour cells express to prevent an immune response
PD-1 receptors
what is the outcome of using anti-PD-1 antibodies
T-cells able to elicit anti-tumour response
function of Bevacizumab (avastin)
targets vascular endothelial growth factor (VEGF)
creates hypoxic conditions surrounding the tumour
what does chemotherapy target
targets all fast-growing cells
what is the function of alkylating agents as a chemotherapeutic
cross-links two DNA strands to prevent DNA replication
function of cisplatin
also cross-links DNA
function of antimetabolites as chemotherapeutics
produce analogous that compete with DNA synthesis
methotrexate - folic acid analogue
5-FU - thymine analogue
cytarabine - pyrimidine analogue
function of plant alkaloids and their mechanism of action
they are mitotic inhibitors
bind to tubulin - interferes with spindle assembly in mitosis
what is the function of the second class of plant alkaloids
topoisomerase inhibitors - inhibits the unwinding of supercoiled DNA
what is the function of antibiotics in terms of chemotherapy
binds non-covalently to DNA
cell cycle stage - non-specific
