Targeted therapy and biologicals

Question 1

CR-ABL tyrosine kinase inhibitors- drugs, used for?

Answer 1

• Imatinib
• Dasatinib
• CML (chrom 9 and 22 translocation)

Question 2

CML- occurs how?

Answer 2

• tyrosine kinase- always active
• ATP cofactor
• protein substrate
• tyrosine phosphorylated substrate

Question 3

Imatinib- moa

Answer 3

-occupies the ATP cofactor binding site on BCR-ABL

Question 4

Dasatinib- used for?

Answer 4

treatment of Imatinib resistant CML!!

Question 5

Imatinib- target tyrosine kinases, therapeutic uses

Answer 5

• BCR-ABL, c-kit, PDGFR

- CML, GIST

Question 6

Dasatinib- target tyrosine kinases, therapeutic uses

Answer 6

• BCR-ABL, Src family

- Resistant CML, ALL (Ph+)

Question 7

GIST- drugs

Answer 7

targets KIT/PDGFRA

• imatinib
• if imatinib resistant- sunitinib

Question 8

Imatinib- adverse effects

Answer 8

-drug interactions due to CYP450 (rifampin and St john’s wort induces CYP45)

Question 9

Breast cancer- what is overexpressed?

Answer 9

HER2

Question 10

Erlotinib, Gefitinib- target tyrosine kinase, cancer use

Answer 10

• EGFR

- NSCLC (non small cell lung cancer)

Question 11

Lapatinib- target tyrosine kinase, cancer use

Answer 11

• EGFR, HER2

- breast cancer

Question 12

Sunitinib- target tyrosine kinase, cancer use

Answer 12

• c-kit, PDGFR, VEGFR

- GIST and RCC

Question 13

Sorafenib- target tyrosine kinase, cancer use

Answer 13

• PDGFR, VEGF (and RAF)

- RCC, HCC

Question 14

Vemurafenib- targets? used for?

Answer 14

• inhibits mutant BRAF V600E

- metastatic malignant melanoma!!

Question 15

EGFR R- Ab treatment, use?

Answer 15

• Cetuximab- colorectal; head and neck (except KRAS mutation)
• Panitumumab- colorectal (except KRAS mutation)

Question 16

HER2 R- Ab treatment, use?

Answer 16

-Trastuzumab- HER2+ breast cancer

Question 17

VEGF ligand- Ab treatment, use?

Answer 17

• Bevacizumab

- RCC

Question 18

why does mutated KRAS determine response to ab’s that inhibit EGFR activation?

Answer 18

by-passes the inhibition of EGFR tyrosine kinase!

downstream of EGFR

Question 19

angiogenesis inhibitors

Answer 19

• ab- bevacizumab

- RTK inhibitors- Sunitinib, sorafenib

Question 20

Bevacizumab- targets?

Answer 20

VEGF ligand (not the R)
-not used for metastatic breast cancer anymore- many SE's

Question 21

why does RCC respond well to angiogenesis inhibitors?

Answer 21

• inactivating mutation of VHL

- VHL normally clears HIFalpha- HIFalpha act VEGF and PDGF

Question 22

RCC- responds to?

Answer 22

• Sunitinib, Sorafenib

- ab- Bevacizumab

Question 23

Rituximab- used for?

Answer 23

-CD20+ B cell lymphoma

Question 24

chemotherapy-induced myelosupression can do what?

Answer 24

neutralize subsequent ab-based therapy!