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31 Cards in this Set
- Front
- Back
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What type of drugs are Imatinib Dastinib
when do we use them? |
BCR-Abl tryosine kinase inhibitors
We use them when there is a t9:22 (CML) because it fuses BCR-Abl which causes continuous tyrosine kinase activity and promotes the continues proliferation of CML cells. |
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MOA of imatinib |
it occupies the ATP cofactor binding site on BCR-Abl which inhibits the transfer of phosphate to tyrosine on substrates.
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When do we use dasatinib |
Treatment for primary and imatinib resistant CML. |
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Resistance of Imatinib |
It targets CML cells but is not curative. Eventually a resistant tumor will emerge.
Resistance is from mutation of ATP binding pocket.
When this happens sue dasatinib |
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What are the target tyrosine kinases which imatinib can inhibit?
what is the therapeutic use? |
BCR-Abl C-Kit PDGFR
Therapeutic use for CML and GIST (GI stromal tumor) |
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What are the target tyrosine kinases which dastinib can inhibit?
Therapeutic use? |
BCR-Abl Src Family
Therapeutic use for imatinib resistant CML and ALL with a philly+ (t9:22) |
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What is GIST? which tyrosine kinases are involved? which tyrosine kinase inhibitors should be used? |
GI stromal tumors 85% of them have either KIT or PDGFR alpha.
use imatinib or in imatinib-resistant GIST use sunitinib. |
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Imatinib drug interactions |
CYP450 drug interactions.
Rifamin and st.john's wort can induce CYP450 and clear imatinib quick. |
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Membrane Associated Receptor Tyrosine Kinase Inhibitors |
Gefitinib Erlotinib Lapatinib Sunitinib Sorafenib |
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How does growth factor receptors tyrosine kinase signaling work |
Growth factors EGF, PDGF, or VEGF bind to receptor tyrosine kinases (in cell membrane) which cause dimeriziation.
The dimeric form then activates down stream signaling like RAS. |
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Which CA is EGFR and ERBB2 (HER2) commonly seen in? |
Breast, Lung, and colorectal
Her2 is expressed in over 25% of breast cancers. Over expression of Her shortens likely hood of survival. |
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Erlotinib and gefitinib -target which tyrosine kinases -used in what CA
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EGFR
NSCLC |
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Lapatinib -target which tyrosine kinases -used in what CA |
EGFR and HER2
Breast CA |
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Sunitinib -target which tyrosine kinases -used in what CA |
C-Kit, PDGFR, VEGFR
GIST and RCC |
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Sorafenib -target which tyrosine kinases -used in what CA |
PDGFR, VEGFR
RCC, HCC |
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What is vemurafenib? what does it do? what is it used for? |
Inhibits mutant BRAF kinase.
It inhibits the down stream signaling of RAS.
Used in metastatic malignant melanoma |
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MOA of antibodies directed against tyrosine kinase signaling |
They either bind to epitopes on growth factors or receptor tyrosine kinases to inhibit binding and activation of tyrosine kinase. |
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Cetuximab and Panitumumab -what are they -what do they inhibit -when are they used? |
They are antibodies which inhibit EGFR receptor
Cetuximab: colorectal, head, and neck CA Panitumumab: Colorectal CA
THEY DO NOT WORK IF THERE IS A KRAS MUTATION. |
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Trastuzumab -what is it -what does it inhibit -when is it used |
antibody which inhibits Her2- Receptor
HER2+ breast CA |
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Bevacizumab -what is it -what does it inhibit -when is it used? |
antibody which inhibits VEGF Ligand
Renal cell carcinoma (can be added to chemo for colon, lung, head and neck) |
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Why does K-RAS interfere with Cetuximab and Panitumumab treatment? |
A mutated RAS can by pass the upstream effect on EGFR.
The mutated RAS will still be on despite inhibition of EGFR |
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Over production of VEGF does what for a tumor? -which drug is an antibody to target it? -which are RTK inhibitors for VEGF? |
It allows tumor angiogenesis which is needed for tumor progression.
Bevacizumab is an antibody which binds to the VEGF ligand so it cannot stimulate angiogenesis.
Sunitinib and sorafenib block the receptor. |
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Why does RCC respond well to angiogenesis inhibitors? |
because typically this CA arises with the VHL tumor suppressor gene mutation.
This allows HIF proteins to accumulated and activate transcription genes for VEGF and PDGF which allow highly vascular tumors to form. |
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Rituxomab -what is it -when do you use it |
CD20 antibody It acts on the exterior surface of the cell and binds to CD20. Used for NHL B-cell lymphoma, and B-cell leukemia (CLL) |
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When Rituxomab binds to the B cells how does it kill them? |
The antibody binds then 1. can recruit complement 2. can recruit NK cells, Tcells, and MQ to kill it 3. can signal self apoptosis |
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Schedule and sequence of antibody therapy |
1. chemotherapy can cause myelosuppression which would then neutralize antibody based therapy if it was given after.
2. antibody therapy can sensitize tumors to concurrent chem. This is important when treating MDR tumors. |
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Bortezomib -targets? -indication -issues |
Target: 26s proteasome Indicated: Multiple Myeloma and Mantle cell lymphoma.
issues: reactivation of varicella zoster. |
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Vorinostat -target -indication -issues |
ORAL target: histone deacetylase inhibitor indicated: cutaneous T cell lymphoma
issues: PE and DVT |
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Anastrazole -target -indication
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target: aromatase inhibitor indication: estrogen dependent breast cancer |
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Exemestane -target -indication |
target: aromatase inactivator
indication: advanced breast cancer |
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aromatase inhibitor MOA |
They interfere with estrogen promoting growth of ER positive breast CA.
Aromatase is needed to make estrogen. They are used mostly in women who have reached menopause because premenopausal women can make enough estrogen to override its effect. |
