Chemo 6

Question 1

What are the Bcr-Abl Tyrosine Kinase inhibitors?

What do they treat?

Answer 1

• Imatinib and Dasatinib

- CML

Question 2

how does Imatinib work?

Answer 2

it occupies the APT cofactor binding site on Bcr-Abl, inhibiting transfer of phosphate to tyrosine on substrates

Question 3

What is Dasatinib used for?

Answer 3

treatment of primary and imatinib resistant CML

Question 4

What is the mechanism of imatinib resistance

Answer 4

-involves mutation of the ATP binding pocket to exclude imatinib

Question 5

Imatinib targets what other tyrosine kinases

Answer 5

-c-kit and PDGFR

Question 6

Dasatinib targets what other tyrosine kinases?

Answer 6

-Src family

Question 7

Imatinib can be used for what cancer other than CML

Answer 7

GIST

Question 8

Dasatinib can be used for what other cancer other than CML

Answer 8

ALL with Ph chromosome

Question 9

85% of GIST tumors contain oncogenic forms of what tyrosine kinases

Answer 9

-KIT or PDGFR

Question 10

What do you use for imatinib resistant GIST

Answer 10

Sunitinib

Question 11

What are the adverse drug reactions with imatinib

Answer 11

due to hepatic CYP450 - rifampin and St. John’s wort hasten the clearance of it

Question 12

HER2 overexpression

Answer 12

Breast cancer

Question 13

What drugs inhibit only EGFR?

used for what cancer?

Answer 13

• Gefitinib
• Erlotinib

-NSCLC

Question 14

What drug inhibits both EGFR and HER2?

What cancer?

Answer 14

Lapatinib

-Breast Cancer

Question 15

what 2 drugs inhibit both PDGFR and VEGFR

Answer 15

• sunitinib

- sorafenib

Question 16

What cancers do you used sunitinib for?

Answer 16

• GIST

- RCC

Question 17

What cancers do you use Sorafenib for

Answer 17

• RCC

- HCC

Question 18

What does Vemurafinib inhibit

Answer 18

-Mutant BRAF V600E

Question 19

what cancer is Vemurafenib used for

Answer 19

metastatic malignant melenoma

Question 20

What are the antibodies that target EGFR receptor?

what cancer?

Answer 20

• Cetuximab (colorectal, head and neck)
• Panitumumab (colorectal)

-don’t work if there is KRAS mutations

Question 21

What is the antibody that targets Her2 receptor?

what cancer?

Answer 21

Trastuzumab

breast with Her2 mutation

Question 22

What is the antibody that targets VEGF LIGAND?

what cancer?

Answer 22

Bevacizumab

RCC

Question 23

why are some cancers with Ras mutation not affected by certain tyrosine kinase inhibitors

Answer 23

they by pass that receptor and affect down stream signal

Question 24

What drug blocks angiogenesis used for advanced solid tumors

Answer 24

Bevacizumab

Question 25

Bevacizumab has been removed from indication for what?

Answer 25

metastatic Breast cancer

Question 26

why does RCC respond well to angiogenesis inhibitors, both drugs (Sunitinib and Sorafenib) and Antibody (Bevacizumab)

Answer 26

they arise from inactivating mutations of BHL which governs the degradation and clarance of HIFa . . so HIF accumulated and activates VEGF and PDGF . . so the angiogenesis inhibitors block VEGF

Question 27

What is Rituxomab used for?

Answer 27

CD20+ B cell Lymphoma

Question 28

Explain the mechanism of action dependent on the number of antibodies that bind?

Why is this a problem?

Answer 28

• few: complement punches holes and flood cell leading to lysis
• moderate: recruits NK, T cells, and macrophages which attack
• Many: Self destruction, apoptosis

chemo induced myelosuppression can neutralize subsequent antibody bases therapy