Targeted Therapies - Fitz

Question 1

How do tyrosine kinase inhibitors work?

Answer 1

Bind to ATP-binding site on TK and prevent enzyme from using ATP to phosphorylate target proteins

Question 2

Imatinib

Answer 2

Bcr-Abl tyrosine kinase inhibitor

Question 3

Dasatinib

Answer 3

Bcr-Abl tyrosine kinase inhibitor (Imatinib-resistance)

Question 4

How does CML become resistant to Imatinib?

Answer 4

Slight mutation of Bcr-Abl TK ATP binding site

Question 5

Imatinib uses

Answer 5

CML, GIST

Question 6

Dasatinib

Answer 6

CML (Imatinib-resistant), [Ph]+ ALL

Question 7

GIST has what TK mutations?

Answer 7

C-Kit, PDGFR

Question 8

EGFR inhibitors

Answer 8

Lapatinib, Gefitinib, Erlotinib

Question 9

HER2 receptor inhibitor

Answer 9

Lapatinib

Question 10

PDGFR/VEGFR inhibitors

Answer 10

Sunitinib, Sorafenib

Question 11

Inhibiting RTKs causes inhibition of what?

Answer 11

Downstream RAS/PI3K, AKT oncogenic signaling

Question 12

EGFR…what cancer?

What drugs?

Answer 12

NSCLC

Erlotinib, Gefitinib

Question 13

EGFR + HER2…what cancer?

What drug?

Answer 13

Breast

Lapatinib

Question 14

C-KIT…what cancer?

What drugs?

Answer 14

GIST

Sunitinib, Imatinib

Question 15

PDGFR, VEGFR…what cancer?

What drugs?

Answer 15

RCC

Sunitinib, Sorafenib

Question 16

BRAF kinase…what cancer?

What drug?

Answer 16

Melanoma

Vemurafinib

Question 17

Anti-EGFR antibody drugs

Answer 17

Cetuximab, Panitumumab

Question 18

Anti-HER2 receptor antibody drug

Answer 18

Trastuzumab

Question 19

Anti-VEGF ligand antibody drug

Answer 19

Bevacizumab

Question 20

Bevacizumab (anti-VEGF) is used in what cancer?

Why is it good in this cancer?

Answer 20

RCC

Prevents angiogenesis, since RCC (VHL mutation) causes VEGF overproduction due to HIF accumulation causes highly vascular tumor

Question 21

If a tumor is K-RAS positive, think what?

Answer 21

Cannot use an RTK inhibitor drug, must think otherwise

Question 22

Rituximab

Answer 22

Anti-CD20 antibody, used for B-cell lymphoma (NHL) and leukemia (CLL)

Question 23

3 “degrees” of Rituximab action on B-cells

Answer 23

• Complement-mediated cell lysis
• NK/T-cell cell lysis
• Apoptosis signal

Question 24

When during treatment should antibody drugs be used?

Answer 24

Before chemo (sensitize tumor) or after (BM recovery 1st)

Question 25

Aromatase inhibitor drugs

Answer 25

Anastrazole, Exemestane

Question 26

When are Aromatase inhibitors beneficial?

Age group?

Answer 26

If the breast cancer is producing estrogen

Post-menopause (ovaries can’t override the estrogen block)