Targeted Therapies - Fitz Flashcards
How do tyrosine kinase inhibitors work?
Bind to ATP-binding site on TK and prevent enzyme from using ATP to phosphorylate target proteins
Imatinib
Bcr-Abl tyrosine kinase inhibitor
Dasatinib
Bcr-Abl tyrosine kinase inhibitor (Imatinib-resistance)
How does CML become resistant to Imatinib?
Slight mutation of Bcr-Abl TK ATP binding site
Imatinib uses
CML, GIST
Dasatinib
CML (Imatinib-resistant), [Ph]+ ALL
GIST has what TK mutations?
C-Kit, PDGFR
EGFR inhibitors
Lapatinib, Gefitinib, Erlotinib
HER2 receptor inhibitor
Lapatinib
PDGFR/VEGFR inhibitors
Sunitinib, Sorafenib
Inhibiting RTKs causes inhibition of what?
Downstream RAS/PI3K, AKT oncogenic signaling
EGFR…what cancer?
What drugs?
NSCLC
Erlotinib, Gefitinib
EGFR + HER2…what cancer?
What drug?
Breast
Lapatinib
C-KIT…what cancer?
What drugs?
GIST
Sunitinib, Imatinib
PDGFR, VEGFR…what cancer?
What drugs?
RCC
Sunitinib, Sorafenib
BRAF kinase…what cancer?
What drug?
Melanoma
Vemurafinib
Anti-EGFR antibody drugs
Cetuximab, Panitumumab
Anti-HER2 receptor antibody drug
Trastuzumab
Anti-VEGF ligand antibody drug
Bevacizumab
Bevacizumab (anti-VEGF) is used in what cancer?
Why is it good in this cancer?
RCC
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
Rituximab
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
Anastrazole, Exemestane
When are Aromatase inhibitors beneficial?
Age group?
If the breast cancer is producing estrogen
Post-menopause (ovaries can’t override the estrogen block)
