Fitzpatrick - Targeted Therapy and Biologicals

Question 1

Bcr-abl inhibitor name and MOA

Answer 1

• Imatibib or Dasintinib (CML tx).

- MOA - Occupies ATP cofactor binding stie on Bcl-abl, inhibiting transfer of phosphate to TK.

Question 2

Tx for Imatinib resistant CML

Answer 2

Dasatinib

Question 3

Selectivity of imatinib v. Dasatinib.

Answer 3

• Imatinib - Bcr-abl c-kit, PDGFR = CML, GIST

- Dasatinib - Bcr-abl, src = CML(imatinib resistant forms), (Ph+)ALL

Question 4

Tx for Imatinib resistant GIST

Answer 4

Sunitinib

Question 5

HER2+ is expressed in 1/4 of ___ cancer

overexpression v expression means what for survival?

Answer 5

breast cancer

Overexpression=3yr survival v. expression=6-7yr survival

Question 6

Drugs that inhibit TK ERB Family signaling/target: HER2 receptor
Drugs that inhibit TK ERB Family signaling/target: EGFR receptor

Answer 6

HER2 = Lapatanib
EGFR2 = Erolotinib, Gefitinib, Lapatinib

Question 7

Drugs that inhibit TK signaling/target: PDGFR receptor, VEGFR receptor

Answer 7

Sunitinib and Sorafenib

Question 8

antibodies to drugs that inhibit EGFR receptors
antibodies to drugs that inhibit HER2 receptors
antibodies to drugs that inhibit VEGF LIGAND

Answer 8

EGFR receptor - PaCe = Panitumumab/Cetiximab
HER2 receptor - LapaTra = Trastuzumab
VEGF-ligand = bevacizumab

Question 9

Vemurafinib inhibits mutant ___

Answer 9

Mutant BRAF V600E = Metastatic Malignant Melanoma

Question 10

Drugs that inhibit TK signaling/target: BCR-Abl

Answer 10

Dasatinib, Imatinib

Question 11

EGFR-receptor target/Cetuximab ab = ___ clinical use

Answer 11

colorectal; H/N (**no KRAS mutation)

Question 12

EGFR-receptor target/panitumumab ab = ___ clinical use

Answer 12

Colorectal cancer (**no KRAS mutation)

Question 13

HER2+ receptor target/trastuzumab ab = ___ clinical use

Answer 13

Breast cancer

Question 14

VEGF ligand target/bevacizumab ab = ___ clinical use

Answer 14

Renal cell carcinoma

Question 15

Why is KRAS a determinant of response to antibodies that inhibit EGFR activation?

Answer 15

Mutant KRAS is permanently activated; bypasses EGFR TK signaling.

Question 16

Name the angiogenesis inhibitors (1 ab and 2 RTK inhibitors)

Answer 16

Ab - bevacizumab (targets a GF LIGAND –> used esp for RCC)

RTK inhibitors - Sunitinib, sorafenib

Question 17

Why does RCC respond well to angiogenesis inhibitors?

Answer 17

Bc arises from mutation in VHL. VHL degrades HIF. Impaired VHL=more HIF=highly vascularized tumor.

Question 18

Rituxomab treats what?

Answer 18

CD20+ B Cell Lymphoma

Question 19

Breast cancer drugs: three

Answer 19

1. Lapatinib/Trastuzumab
2. Anastrazole (aromatase inhibitor = reversible)
3. Exemestane (aromatase inactivator = irreversible)

Question 20

NSCLC drugs

Answer 20

(EGFR) Erlotinib, Gefitinib

Question 21

Breast Cancer

Answer 21

Lapatinib - EGFR and HER2

Question 22

GIST and RCC

Answer 22

Sunatinib (c-kit, PDGFR, VEGFR)

Question 23

RCC and HCC

Answer 23

SoRAFenib (PDGFR, VEGFR)