Flashcards in Fitzpatrick - Targeted Therapy and Biologicals Deck (23):
Bcr-abl inhibitor name and MOA
- Imatibib or Dasintinib (CML tx).
- MOA - Occupies ATP cofactor binding stie on Bcl-abl, inhibiting transfer of phosphate to TK.
Tx for Imatinib resistant CML
Selectivity of imatinib v. Dasatinib.
- Imatinib - Bcr-abl c-kit, PDGFR = CML, GIST
- Dasatinib - Bcr-abl, src = CML(imatinib resistant forms), (Ph+)ALL
Tx for Imatinib resistant GIST
HER2+ is expressed in 1/4 of ___ cancer
overexpression v expression means what for survival?
Overexpression=3yr survival v. expression=6-7yr survival
Drugs that inhibit TK ERB Family signaling/target: HER2 receptor
Drugs that inhibit TK ERB Family signaling/target: EGFR receptor
HER2 = Lapatanib
EGFR2 = Erolotinib, Gefitinib, Lapatinib
Drugs that inhibit TK signaling/target: PDGFR receptor, VEGFR receptor
Sunitinib and Sorafenib
antibodies to drugs that inhibit EGFR receptors
antibodies to drugs that inhibit HER2 receptors
antibodies to drugs that inhibit VEGF LIGAND
EGFR receptor - PaCe = Panitumumab/Cetiximab
HER2 receptor - LapaTra = Trastuzumab
VEGF-ligand = bevacizumab
Vemurafinib inhibits mutant ___
Mutant BRAF V600E = Metastatic Malignant Melanoma
Drugs that inhibit TK signaling/target: BCR-Abl
EGFR-receptor target/Cetuximab ab = ___ clinical use
colorectal; H/N (**no KRAS mutation)
EGFR-receptor target/panitumumab ab = ___ clinical use
Colorectal cancer (**no KRAS mutation)
HER2+ receptor target/trastuzumab ab = ___ clinical use
VEGF ligand target/bevacizumab ab = ___ clinical use
Renal cell carcinoma
Why is KRAS a determinant of response to antibodies that inhibit EGFR activation?
Mutant KRAS is permanently activated; bypasses EGFR TK signaling.
Name the angiogenesis inhibitors (1 ab and 2 RTK inhibitors)
Ab - bevacizumab (targets a GF LIGAND --> used esp for RCC)
RTK inhibitors - Sunitinib, sorafenib
Why does RCC respond well to angiogenesis inhibitors?
Bc arises from mutation in VHL. VHL degrades HIF. Impaired VHL=more HIF=highly vascularized tumor.
Rituxomab treats what?
CD20+ B Cell Lymphoma
Breast cancer drugs: three
2. Anastrazole (aromatase inhibitor = reversible)
3. Exemestane (aromatase inactivator = irreversible)
(EGFR) Erlotinib, Gefitinib
Lapatinib - EGFR and HER2
GIST and RCC
Sunatinib (c-kit, PDGFR, VEGFR)