Antineoplastics V

Question 1

Signal transduction inhibitor drugs

Answer 1

• Imatinib, erlotinib, gefitinib

- Bind to ATP-binding site of tyrosine kinases

Question 2

Tyrosine kinases

Answer 2

-important regulators of intracellular signal transduction pathways, where they are involved in development and multicellular communication
they phosphorylate tyrosine residues
-over 1000 different tyrosine kinases have been identified

Question 3

Bosutinib, Dasatinib, imatinib, nilotinib MOA

Answer 3

• competitive antagonists of ATP binding site of: BCR-ABL, C-kit, PDGF (weak).
• Dasatinib also targets Src

Question 4

Bcr-abl

Answer 4

non-receptor tyrosine kinase disregulated by the translocation of its gene from chromosome 9 to chromosome 22 in most patients withCML

Question 5

C-kit

Answer 5

tyrosine kinase altered in gastrointestinal stromal tumours (GI Stromal Tumor treatment)

Question 6

Src

Answer 6

Tyrosine kinase whose expression is upregulated in several types of cancer

Question 7

Erlotinib and Gefitinib MOA

Answer 7

competitive antagonists of theATP-binding siteofepithelial growth factor receptor (EGFR) tyrosine kinase, which is overexpressed in a large number ofepithelial-derived cancers

Question 8

Resistance in tyrosine kinase inhibitors

Answer 8

• -Change in target proteins
• -Usually secondary resistance due to mutation of ATP binding in cancer cells
• -Sometimes of overexpression of bcr/abl or expression of other kinases

Question 9

Why were bosutinib, dastinib, nilotinib developed?

Answer 9

To target cells that have become resistant to imatinib

Question 10

Pharmacokinetics of tyrosine kinase inhibitors

Answer 10

• -oral administration; good bioavailability
• -highly plasma protein bound
• -metabolized in the liver (CYP 3A4), and excreted in the feces (hepatobiliary excretion)

Question 11

Boutinib, imatinib, datatinib, nalotinib uses

Answer 11

• -complete hematological and cytological response in85-95%of patients in thechronic phase of CML
• -delay death in 25% of patients in blast crisis(75% of these patients initially respond)
• -gastrointestinal stromal tumoursexpressingc-kit

Question 12

Erlotinib and gefitinib uses

Answer 12

• -metastatic non-small cell lung cancer (NSCLC) after failure of standard chemotherapies
• -different populations experience varying efficacies

Question 13

Toxicity for STIs

Answer 13

• -generally relatively minor side effects: nausea, vomiting, fatique, myalgia, diarrhea, skin rashes and acne, drug interactions
• -Can cause CHF and/or MYOCARDIAL INFARCTION
• -More common in dasatinib, imatinib, nilotinib.
• -Teratogenic

Question 14

Imatinib toxicity (specific)

Answer 14

edema, bone marrow suppression

Question 15

Erlotinib and gefitinib toxicity (specific)

Answer 15

Rare INTERSTITIAL PNEUMONIA (which can be fatal)

Question 16

How long do you have to take these drugs for the cancer to go away?

Answer 16

Forever. If stop taking, the cancer will return. It isn’t a cure. Turning the cancer into a chronic disease.