Drugs Targeting Protein Function Flashcards
What drugs inhibit EGFR?
Cetuximab, Erlotinib, Gefitinib, Panitumumab
What drugs inhibit HER2?
Pertuzumab, Trastuzumab
What do tyrosine kinases do?
regulators of intracellular signal transduction pathways
What role do Tyrosine kinases play in cancer?
TK receptors are often mutated or overexpressed in cancers
-signal transduction inhibitors and abs made to target these
What is overexpressed in many epithelial-derived cancers?
EGFR
What is the MOA for Cetuximab and Panitumumab?
Mabs against EGFR to prevent actions of EGFR + identify cells that express the receptor for degradation
What are the unique toxicities associated with Cetuximab and Panitumumab?
skin (rash, photosensitivity, necrotizing fasciitis), lung (interstitial lung disease)
What is the MOA for Trastuzumab?
interferes with Her2 signaling + identifies Her2-overexpressing cells for degradation
What is the MOA for pertuzumab?
dimerization inhibitor - prevents Her2 from dimerizing with other HER receptors
What is the MOA for Ado-Trastuzumab Emtansine?
internalized and degraded in lysosomes to form Trastuzumab + DM1 (inhibits microtubules by binding tubulin)
What resistance forms to Trastuzumab/pertuzumab?
altering Her2 so ab cannot recognize it
What are the toxicities of Trastuzumab?
infusion/hypersensitivity rxns, infections, birth defects/fetal loss
unique: ventricular dysfunction and CHF
What is the major difference between drugs that target mutated/overexpressed proteins and drugs that target altered intracellular processes?
the later tends to be less specific for cancer - more AE
What is the mechanism that L-asparaginase uses to deplete asparagine?
asparagine is converted to aspartate so that cancer cells cannot directly transport asparagine into the cell –> die due to lack of asparagine
How does L-asparaginase have selective toxicity?
ALL cancer cells lack asparagine synthase, so they cannot transport aspartate; normal cells can transport aspartate
Why is L-asparaginase often given with Mtx?
Mtx given FIRST, L-asparaginase given SECOND has synergistic cytotoxicity (more total cells killed than using either alone; timing matters)
What drugs inhibit proteosomes?
Bortezomib, Carfilzomib
What is the MOA for Bortezomib/ Carfilzomib?
inhibit the 26S proteosome –> triggers apoptosis
What are the toxicities associated with Bortezomib/ Carfilzomib?
thrombocytopenia, neutropenia, anemia, peripheral neuropathy
What drugs inhibit HDACs?
Romidepsin, Vorinostat
What is the MOA for Romidepsin, Vorinostat?
inhibit HDAC –> increase transcription –> cell cycle arrest and apoptosis result
What do HDACs do in cancer?
work with HAT to regulate gene expression - cancer cells can overexpress/recruit HDACs –> prevent transcription –> silence tumor suppressor genes
What are toxicities associated with Romidepsin/ Vorinostat?
Hemato: PE, DVT
Drug-Drug interactions: valproic acid, Warfarin (causes warfarin to increase - bleeding)
What are the drugs that induce differentiation?
Tretinoin (Atra, Retin-A), Arsenic Trioxide (ATO), Bexarotene
