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25 Cards in this Set
- Front
- Back
- 3rd side (hint)
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Who would benefit from Iressa treatment?
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1) Lung and breast cancer patients who overexpress EGFr-erbB1/HER1??????? 2) adenocarcinoma and bronchoalveolar carcinoma 3) responders got rash… 4) non-smokers.
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Does Iressa improve the response to other chemotherapy?
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no
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What is the mechanism of action of Iressa?
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binds to the tyrosine kinase domain and blocks ATP binding on the TKR
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What are the notable toxicities of Iressa?
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Diarrhea, rash and acne
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What is the receptor target for Iressa?
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EGFr erbB1/HER1
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None
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In general, what are 2 things we consider in pharmacogenetics?
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1. Is there a viable target (is that target something being misexpressed or overexpressed in a patient)… 2. Variability in drug metabolism of enzymes (Does the patient over or under-metabolize the drug, e.g., toxicity or active metabolite)
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What two pharmacogenomics do we consider in EGFr inhibiting cancer drugs?
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Expression of EGF receptor, and a metabolism consistent with drug metabolite
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What mechanism would explain the response of some patients to Iressa?
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Responder have a mutation in the ATP binding site of the EGFr tyrosine kinase domain… 2) these mutated EGF receptors respond are inhibited more compared to wild-type receptors… 3) mutant EGF receptors are constitutively active
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In which cases does Iressa work best?
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Gene amplification?
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Does Iressa prolong life?
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no
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While Iressa does not prolong life for lung cancer patients, what drug does prolong life?
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Erlotinib (which is similar to Iressa)
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None
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Which cancer type is Alimta suggested for treatment?
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Lung: Mesothelioma and non-small cell lung cancer
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What is used in combination with Alimta for treatment of Mesothelioma?
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Cisplatin
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What is used in combination with Alimta for treatment of non-small cell lung cancer?
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None… Alimta is used as a single agent
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Why, if Alimta and Docetaxol have similar response rate, is Alimta preferred? (three reasons)
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1. less leukopenia and neutropenia… 2. Less febrile netruopenia… 3. Less infection with grade 3/4 neutropenia
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How is RAS important in explaining why Iressa may not work?
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If RAS is constitutively active it doesn’t matter what you do to the receptor protein tyrosine kinase, because RAS is downstream.
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Who would benefit from Herceptin treatment?
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Breast cancer patients that overexpressed erbB2 Receptor
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What kind of receptor is the erbB2 Receptor?
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Heterodimerizing-activating TKR
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What receptor does Iressa target?
What is the two step mechanism of Iressa? What is also believed to be inhibited by Iressa? |
1) erbB2/Her2
2) mAb binds the erbB2 receptor kinase domain --> followed by CdK inhibition 3) Herceptin may also suppress angiogenesis |
None
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Who would benefit from Tamoxifen treatment?
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breast cancer patients that overexpressed estrogen receptors
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What is the mechanism of action of Tamoxifen?
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Competitive inhibitor of estrogen @ estrogen receptors
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What are the proposed mechanisms of action for EGFr tyrosine kinase inhibitors? (hint: 5 decrease, and 2 increase)
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reduces: proliferation, invasion, metastasis, agiogenesis, and adhesion… Increases: apoptosis and sensitivity to chemotherapy.
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What would explain why non-smokers responded to Iressa?
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Their cancer may have arisen primarily due to EGFr tyrosine kinase overexpression
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What type of mutation is seen in the EGFR of Iressa (Gefitinib) responders?
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Mutation in the tyrosine kinase (ATP) binding site
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What type of cancers respond to Iressa? (Hint: histopathology)
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Adenocarcinoma of lung, and Bronchioalveolar carcinoma
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None
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