Tyrosine Kinase Inhibitors Flashcards
What protein function inhibitor drugs target a unique aspect of specific cancer type?
L-asparaginase
Imatinib
What protein function inhibitors are less specific and exploit overexertion of a particular protein?
Erlotinib
Gefitinib
What protein function inhibitors are targeting rapidly dividing cells and/or angiogenesis?
Bortezomib
Vorinostat
Sorafenib
Sunitinib
What are the types of Tyrosine kinase inhibitors?
- Some are Signal Transduction Inhibitors
- Inhibitors of:
1. Bcr-Abl
2. EGFR
3. HER2
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?
-Bosutinib
-Dasatinib
-Imatinib
-Nilotinib
CML (chronic myeloid leukemia)
What drugs are tyrosine kinase inhibitors of EGFR? What type of cancer are they used for?
-Cetuximab
-Erlotinib
-Gefitinib
-Panitumumab
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?
-Pertuzumab
-Trastuzumab [Ado-Trastuzumab, Emtansine]
Breast cancer
What drugs are tyrosine kinase inhibitors of PDGF-R, VEGF-R? (not talking about these) What are these used for?
-Pazopanib
-Sorafenib
-Sunitinib
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?
- Dasatanib
- Imatinib
- Nilotinib
- Sunitinib
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)»_space; Chimeric (XI) > Humanized (ZU) for HAMA reaction
- –Infections
- –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!
