Flashcards in Targeted Therapies - Fitz Deck (26):
How do tyrosine kinase inhibitors work?
Bind to ATP-binding site on TK and prevent enzyme from using ATP to phosphorylate target proteins
Bcr-Abl tyrosine kinase inhibitor
Bcr-Abl tyrosine kinase inhibitor (Imatinib-resistance)
How does CML become resistant to Imatinib?
Slight mutation of Bcr-Abl TK ATP binding site
CML (Imatinib-resistant), [Ph]+ ALL
GIST has what TK mutations?
Lapatinib, Gefitinib, Erlotinib
HER2 receptor inhibitor
Inhibiting RTKs causes inhibition of what?
Downstream RAS/PI3K, AKT oncogenic signaling
EGFR + HER2...what cancer?
PDGFR, VEGFR...what cancer?
BRAF kinase...what cancer?
Anti-EGFR antibody drugs
Anti-HER2 receptor antibody drug
Anti-VEGF ligand antibody drug
Bevacizumab (anti-VEGF) is used in what cancer?
Why is it good in this cancer?
Prevents angiogenesis, since RCC (VHL mutation) causes VEGF overproduction due to HIF accumulation causes highly vascular tumor
If a tumor is K-RAS positive, think what?
Cannot use an RTK inhibitor drug, must think otherwise
Anti-CD20 antibody, used for B-cell lymphoma (NHL) and leukemia (CLL)
3 "degrees" of Rituximab action on B-cells
- Complement-mediated cell lysis
- NK/T-cell cell lysis
- Apoptosis signal
When during treatment should antibody drugs be used?
Before chemo (sensitize tumor) or after (BM recovery 1st)
Aromatase inhibitor drugs