Appel

Question 1

What are the two types of targeted therapies?

Answer 1

Tyrosine Kinase inhibitors and Monoclonal Antibodies

Question 2

What IS targeted therapy?

Answer 2

Drug targets biological process that is measurable and correlates with clinical outcome. drug is less toxic to normal cells.

Question 3

What is the MOA of Imatinib?

Answer 3

Occupies the ATP binding pocket of the Abl kinase domain. Prevents substrate phosphorylation and signaling.

Question 4

How do monoclonal antibodies work?

Answer 4

Bind to ligands or receptors interrupting essential cell processes. carry lethal radioisotope or toxin. Recruit host immune factors including NK cells and complement cascade.

Question 5

What is VEGF?

Answer 5

Vascular endothelial growth factor… activates blood vessel growth. Tumor uses to recruit a blood supply!

Question 6

Bevacizumab MOA?

Answer 6

Binds directly to the VEGF ligand and prevents activation of receptors to inhibit angiogenesis.
(mab)
FOR METASTIC DISEASE

Question 7

What is the major difference between the actions ofmonoclonal ABs and TKIs?

Answer 7

TKIs are much less specific!

bind intracellularly! also have a longer half life and metabolized by p450

Question 8

Why is sunitinib a dirty molecule?

Answer 8

Targets LOTS! vegf, pdgf, c-kit, flt-3

Question 9

Sunitnib MOA?

Answer 9

TKI! inhibits signal transduction intracellularly, chiefly vegr-2…. inhibits endothelial cell migration, prolif, differentiation, survival, vessel permeability.

Question 10

Sunitinib is most often indicated for….?

Answer 10

Kidney Cancer!

Question 11

WHat are the drugs that target angiogenesis? both MAB and TKI

Answer 11

Imatinib, Bevacizumab, Sunitinib

Question 12

Why target the EGFR axis?

Answer 12

In tumor cells, EGFR-TK signal is inappropriately turned on! activity drives uncontrolled growth.

Question 13

What is the most common anti EGFR TKI?

Answer 13

Erlotinib!!
Lung cancer
tox- rash + diarrhea

Question 14

What is the MOA for cetuximab?

Answer 14

High affinity Ab binds to EGFR to block ligand induced phosphorylation of EGFR. blocks cell prolif and promotes apoptosis.
tox- rash with pustules
COLORECTAL CANCER

Question 15

Which monoclonal antibody binds to the HER2 extracellular domain?

Answer 15

Trastuzumab! prevents activation of HER2’s intracellular tyrosine kinase.
decreased signaling decreases prolif, adhesion, migration, differentiation.
for BREAST CANCER

Question 16

How can we predict Trastuzumab response?

Answer 16

We can measure HER2 overexpression!

Question 17

Lapatinib?

Answer 17

Oral! inhibits intracellular signaling by HER1 and HER2! ADVANCED BREAST CANCER

Question 18

What drug offers a dual blockade in advanced breast cancer?

Answer 18

Pertuzumab~

heterodimerization and homodimerization (her2 and3)

Question 19

What is the mechanism of Rituximab?

Answer 19

Antibody dependent cell mediated cytotoxicity (ADCC) Induces B cell death, anti-CD20 monoclonal antibody! (cd20 on PRE-B)
LYMPHOMA!!!!!

Question 20

How do we choose a target antigen?

Answer 20

Should be highly expressed in tumor cells, NOT expressed in normal cells, present on SURFACE, should be internalizing

Question 21

Antibody should be…?

Answer 21

specific to target, limited immungenecity, have good affinity

Question 22

Linker should be…

Answer 22

stable in circulation so not released systemically into normal cells! should bind agent until ADC internalized!