BIOLOGICS Flashcards
small molecule inhibitors and biologics
cetuximab
Cetuximab is a chimeric (mouse/human) Mab that
binds to and inhibits EGFR (HER1)
trastuzumab
humanised Mab targeting HER2
bevacizumab
binds to vascular endothelial growth
factor (VEGF-a) preventing it from binding to its
receptor
moa of trastuzumab (inhibition of tumour proliferation)
Binding of Trastuzumab to HER2 prevents it dimerising
and signalling
* Stimulates HER2 receptor downregulation by promoting
its endocytosis and proteolysis limiting the signal for
further cell growth
moa of trastuzumab (prevention of activation)
Prevents shedding of the extracellular portion of the receptor by inhibiting the action of
metalloproteinases
types of her 1 receptor tki
gefitinib
afatinib
osimertinib
gefitinib
1st generation reversible binding
to wildtype and mutated receptors
afatinib
2nd generation irreversible binding
to wildtype and mutated receptors
osimertinib
- 3rd generation irreversible
binding to receptors with the resistance
mutation T790M
types of kinase inhibitors
vemurafenib
trametinib
vemurafenib
B-RAF kinase inhibitor with selectivity for the
ATP binding site with the V600E mutation
(constitutively active) inhibiting the kinase
activity
* CYP1A2 inhibitor; CYP3A4 inducer
trametinib
Reversible MEK1 and MEK2 kinase inhibitor
* Binds to S218 in the activation loop of the
enzyme preventing phosphorylation by RAF at
this residue
what are types of cancer immunotherapy
rituximab
blimatumomab
ipilimumab
nivolumab
atezolizumab
rituximab (chimeric)
Directed against CD20 expressed on B cells
* Recruits macrophages, natural killer cells, complement
proteins for cell destruction
Ofatumumab (human)
Directed against CD20 expressed on B cells
* Recruits macrophages, natural killer cells, complement
proteins for cell destruction
blinatumomab (human)
A bi-specific antibody composed of 2 variable regions which
recognise CD19 (B cell) and CD3 (CD8+ T cell )
* Tethers the cancerous B cells to cytotoxic T cells promoting
their destruction
ipilimumab (human)
binds to CTLA-4.
* CTLA-4 is an inhibitory protein expressed on the surface of
activated T cells. It binds to C80/86 to downregulate T cell
function
nivolumab (human)
binds to PD-1 preventing PD-1L binding
to it
atezolizumab (humanised)
binds to PD-1L
* PD-1 limits the activation of immune cells. When PD-1L binds to
PD-1 it triggers prompt apoptosis of the T cell
* Checkpoint inhibitors act to increase the immune response.
types of Poly ADP Ribose Polymerase (PARP)
Inhibitors
Poly ADP ribose polymerase (PARP) inhibitors e.g. Olaparib and Niraparib
* Inhibit repair of single strand breaks in DNA