TKIs

Question 1

TKI drug names (4)

Answer 1

dasatinib
nilotinib
bosutinib
ponatinib

Question 2

TKI MOA

Answer 2

inhibits BCR-ABL oncoprotein

inhibits RTK for platelet derived growth factor receptor PDGFR and c-KIT

Question 3

TKI AE

Answer 3

acute- vomiting, nausea

delated -fluid retention, ankle periorbital edema, diarrhea, myalgias, congestive heart failure

Question 4

TKI clinical apps

Answer 4

CML (phill chrom 9;22)
first line therapy in chronic phase CML
blast crisis
second line for chronic phase CML that has progressed on prior IFN alpha therapy
GI stromal tumors expressing c-KIT TKI

Question 5

dasatinib

Answer 5

inhiits bcr abl, c kit, pdgfr beta tyrosine kinases

differs from imatinib because it binds to bcr-abl during active and inactive conformations of the domain overcomes imatinib resistant resulting from bcr-abl resistance

Question 6

nilotinib

Answer 6

inhibits bcr abl, c kit, pdgfr beta tyrosine kinases

higher affinity to abl kinase than imatinib, overcomes the bcr-abl mutations causing imatinib resistance

clinical: first line tx for chronic phase CML

Question 7

bosutinib

Answer 7

bcr-ABL TK inhibitor
AEs: nausea, vomiting, fluid retention, myelosuppresison, skin rash, hepatoxicity

adult patients with chronic, accelerated, or blast phase Ph chromosome positive CML with resistance or intolerance to prior therapy

Question 8

ponatinib

Answer 8

bcr-abl inhibitor, vegfr-r, pdgf, fgf, Flt3, TIE-2, Src family kinases, Kit, TET, EPH

inhibits all known forms of bcr ABL mutation

clinical: adult pts with chronic, accelerated, or blast phase CML resistant/intolerant to prior TKI therapy. Also approved for Ph+ ALL that is resistant or intolerant to prior TKI therapry