Medical Pharmacology Practice Questions: BCR-ABL Kinase Fusion Gene Inhibitors: Imatinib, Dasatinib, Nilotinib
I
Click on the correct answer.
The Philadelphia chromosome translocation t (9;22) results in expression of ABL and BCR. The result of this gene fusion is a continually active protein kinase, BCR-ABL
True
False
BCR-ABL, the fusion gene, drives the cancer phenotype of chronic myelogenous leukemia (CML):
True
Vaules
Imatinib mesylate (Gleevec) inhibits the BCR-ABL tyrosine kinase fusion protein, the product of this driver mutation.
True
False
About 50% of patients with CML in the chronic disease phase may achieve remission following administration of imatinib and related second-generation inhibitors.
True
False
In comparing imatinib and dasatinib,
Imatinib inhibits BCR-ABL kinase
Dasatinib inhibits BCR-ABL kinase and Src kinase, a non-receptor tyrosine kinase involved in several human cancers.
Both
Neither
Nilotinib pharmacology:
Compared to imatinib, nilotinib seems to exhibit enhanced potency and specificity
Nilotinib does not appear susceptible to drug resistance of the type seen with imatinib.
True
False
Imatinib, dasatinib, and nilotinib appear similar in inhibitory potency, binding specificity and drug resistance to kinase mutations.
True
False
Both
Neither
The principal therapeutic aim(s) in using BCR-ABL kinase inhibitors in chronic myelogenous leukemia:
Complete cytogenetic response and a very significant molecular response in CML
The "major molecular response (MMR)" aim is defined as BCR-ABL RNA < 0.1 %.
Both
Neither
Adverse effects/effects associated with BCR-ABL inhibitors:
Myelosuppression
Fatigue
Both
Neither
If drugs that inhibit or induce the cytochrome P450 drug metabolizing isoform CYP3A4 are coadministered with a BCR-ABL kinase inhibitor, dosage changes may be required. Furthermore, it may be necessary to avoid use of such inducers or inhibitors.
