Flashcards in Tyrosine Kinase Inhibitors Deck (19)
What protein function inhibitor drugs target a unique aspect of specific cancer type?
What protein function inhibitors are less specific and exploit overexertion of a particular protein?
What protein function inhibitors are targeting rapidly dividing cells and/or angiogenesis?
What are the types of Tyrosine kinase inhibitors?
-Some are Signal Transduction Inhibitors
4. PDGF-R, VEGF-R (not talking about these)
What drugs are tyrosine kinase inhibitors of Bcr-Abl? What cancer type are they used for?
CML (chronic myeloid leukemia)
What drugs are tyrosine kinase inhibitors of EGFR? What type of cancer are they used for?
Epithelial derived (lung, pancreas, head, neck, breast, prostate, colon, stomach, ovaries, brain)
What drugs are tyrosine kinase inhibitors of HER2? What cancer are these used for?
-Trastuzumab [Ado-Trastuzumab, Emtansine]
What drugs are tyrosine kinase inhibitors of PDGF-R, VEGF-R? (not talking about these) What are these used for?
Many different cancers - including glioblastoma, hepatocellular carcinoma, renal cell carcinoma
What doe the -nib ending mean?
Signal transduction inhibitor
What are some important general concepts about tyrosine kinases?
-TKs are important regulators of intracellular signal transduction pathways responsible for development and multicellular communication
-TKs phosphorylate tyrosine residues
->50% of known receptor TKs have been found either mutated or overexpresssed forms that are associated with malignancies
-Both STI and antibodies have been designed to interfere with the action of specific tyrosine kinases
What drugs target c-kit and fight GIST (gastrointestinal stromal tumor) cancer?
What is the MOA for Cetuximab/Panitumumab?
Inhibitors of EGFR
-Epithelial Growth Factor Receptor (EGFR) tyrosine kinase is overexposed in a large number of epithelial-derived cancers
-These drugs are monoclonal antibodies directed against EGFR
-These drugs prevent actions of EGFR, as well as identifying cells expressing the receptor as foreign (making them targets of cell mediated immunity)
What are the side effects of cetuximab/panitumumab?
-Side effects common to Abs:
---Infustion/hypersensitivity reactions: fever, muscle aches, headaches, rashes, anaphylaxis, infusion reactions
---Mouse (MO) >> Chimeric (XI) > Humanized (ZU) for HAMA reaction
---Unknown effects on immunization, carcinogenesis, mutagenesis, impairment of fertility, pregnancy, nursing infants (human IgG is secreted in milk)
-Unique toxicities affect skin (rash, photosenstivity, necrotizing fasciitis) and lung (interstitial lung disease)
How do HER1 inhibitors affect cancer?
Human Epithelial Growth Factor Receptor 2 tyrosine kinase is overexposed in a large number of aggressive breast cancers
-Mostly used for breast cancers that you can't use doxorubicin to target!!
What is the mechanism of trastuzumab?
Binding of the antibody interferes with HER2 signaling, and identifies the HER2-overexpressing cells as foreign, so that they can be destroyed by the immune system!
What is the mechanism of action of Perfuzumab?
It's considered the first antineoplastic DIMERIZATION INHBIITOR (new drug class) ; it prevents HER2 from dimerizing with other HER receptors (can't function)
What is the mechanism of action of Ado-Trastuzumab Emtansine?
It is internalized and undergoes lysosomal degradation to form 2 parts:
2. DM1 - a small molecule inhibitor that disrupts microtubule networks by binding tubulin
What is the resistance mechanism developed against HER2 inhibitors?
Altering HER2 so that the antibody doesn't recognize its target!!