Targeted Drugs

Question 1

Imatinib (Gleevec)

Answer 1

BCR-ABL (TK fusion- constitutive activation)

small molecule; PO

Question 2

Crizotinib (Xalkori)

Answer 2

ALK (TK fusion - constitutive activation)

small molecule; PO

Question 3

Erlotinib (Tarceva)

Answer 3

EGFR (TKR mutation- constitutive activation)

Question 4

Dasatinib (Sprycel)

Answer 4

BCR-ABL (TK fusion - constitutive activation)

small molecule; PO

Question 5

Nilotinib (Tasigna)

Answer 5

BCR-ABL (TK fusion - constitutive activation)

small molecule; PO

Question 6

Alectinib (Alecensa)

Answer 6

ALK (TK fusion - constitutive activation)

small molecule; PO

Question 7

osimertinib (Tagrisso)

Answer 7

EGFR - TKR mutation- constitutive activation)

Question 8

Dabrafenib (Tafinlar)

Answer 8

BRAF V600E (TK mutation - constitutive activation)

Question 9

Trametinib (Mekinist)

Answer 9

MEK (TKr mutation - constitutive activation)

Question 10

Trastuzumab (Herceptin)

Answer 10

HER-2 (TKr overexpression)

Question 11

Cetuximab (Erbitux)

Answer 11

EGFR (TKr overexpression)

Question 12

Ibrutinib (Imbruvica)

Answer 12

BTK (TKr overexpression)

Question 13

Bevacizumab (Avastin)

Answer 13

VEGF (angiogenesis)

Question 14

Sorafenib (Nexavar)

Answer 14

VEGFR/PDGFR (angiogenesis)

Question 15

Sunitinib (Sutent)

Answer 15

VEGFR/PDGFR (angiogenesis)

Question 16

TK fusion (chromosomal translocation) targets

Answer 16

BCR-ABL

ALK

Question 17

TK receptor Tyr mutation (constitutive activation) targets

Answer 17

EGFR
BRAF, MEK
KIT

Question 18

Overexpression of receptor TK or ligand targets

Answer 18

HER-2
EGFR
BTK

Question 19

VHL, HIF associated with which hallmark

Answer 19

induce tumor angiogenesis

Question 20

BCR-ABLi resistance (5)

Answer 20

1. efflux MDR1
2. plasma protein binding
3. drug target mutation RIP… switch drug
4. constitutive activation of downstream
5. BCR-ABL gene amplification

Question 21

KRAS affects what

Answer 21

EGFR. Cetuximab won’t work

Question 22

-tinib

Answer 22

TK inhibitor

Question 23

-brutinib

Answer 23

TK inhibitor (BTK)

Question 24

-ertinib

Answer 24

EGFR inhibitor

Question 25

-metinib

Answer 25

TK inhibitor (MEK)

Question 26

-rafenib

Answer 26

RAF kinase inhibitor

Question 27

-anib

Answer 27

angiogenesis inhibitor

Question 28

-ciclib

Answer 28

cyclin dependent kinase inhibitor

Question 29

-toclax

Answer 29

BCL-2 inhibitor

Question 30

-parib

Answer 30

PARP inhibitor

Question 31

-sidenib

Answer 31

IDH inhibitor

Question 32

2 families of TKs

Answer 32

Receptor TKs - transmembrane: extracellular and intracellular (receptor or ligand bound) Non-receptor TKs- intracellular (small molecule; PO)

Question 33

BCR-ABL inhibitor binding

Answer 33

ATP pocket

Question 34

MEK activation

Answer 34

frequent cause of resistance. Give BRAF-1 and MEK inhibitor to prevent

Question 35

Mechanisms of TK dysregulation

Answer 35

1. Fusion - constitutive activation 2. Mutations - constitutive activation 3. Overexpression of RTK (or its ligand)

Question 36

Mechanism of BCL-2 inhibitors

Answer 36

1. Drug restores apoptosis by blocking anti-apoptotic signals 2. BH3 mimetic

Question 37

PARP inhibitors and BRCA mutations

Answer 37

PARP -cause ss breaks ``` Active BRCA (both or 1) - fixes ds breaks Lack BRCA 1 & 2 - can't repair ds breaks *PARP indicated for BRCA 1 & 2 mutation* ```

Question 38

KRAS mutations

Answer 38

predicts for resistance (mutation) | * biomarker

Question 39

Unexpected ADEs of targeted therapy

Answer 39

- skin rash (EGFR) - cardiotoxicity (trastuzumab) - Vascular (bevacizumab) - Hand foot skin reaction - Hypothyroidism

Question 40

EGFR rash

Answer 40

occurs in 50-100% of patients!

Question 41

Targeted therapy overall effect on survival

Answer 41

rapid, short-lived tumor responses | doesn't improve survival; relapse & resistance generally occurs