Targeted Therapies- Antineoplastic

Question 1

How do BCR-ABL inhibitors work?

Answer 1

Block TK, which blocks the downstream pathway that leads to cell proliferation

Question 2

What does a Philadelphia Chromosome translocation lead to?

Answer 2

An expression of BCR and ABL, leading to unctrollable cell proliferation

Question 3

What cancer is the Philadelphia chromosome closely related to?

Answer 3

Chronic myeloid leukemia

Question 4

What are the BCR-ABL tyrosine kinase inhibitors?

Answer 4

Imatinib, Dasatinib, nilotinib

Question 5

What it unique about dasatinibs ability compared to others in its class?

Answer 5

It can inhibit many TKs, but it can overcome Imatanib resistance

Question 6

Which has higher binding affinity to Abl, Nilotinib or Imatinib?

Answer 6

Nilotinib

Question 7

What are the Multi kinase RTKs Inhibitors?

Answer 7

Sunitinib, sorafenib, pazopanib

Question 8

What do the Muli kinase RTKs inhibitors do?

Answer 8

Inhibit multiple receptor kinasases

Question 9

What is the action of epidermal growth factor receptors?

Answer 9

Leads to cell proliferation, invasion, metastasis, and angiogenesis
This is overexpressed in several solid tumors

Question 10

What is the murine percent of Mouse (omab)?
Chimeric (Ximab)?
Humanize (zumab)?
Human (umab)? Human

Answer 10

100%
33%
10%
100%

Question 11

What is cetuximabs MOA?

Answer 11

chimeric mAb directed against extracellular EGFR domain

Question 12

What can we know by looking at cetuximabs name?

Answer 12

xi, so highest murine content, so definitely hypersensitivity problems

Question 13

What is critical to know about cetuximabs administration?

Answer 13

Should not be given with radiation of head/neck, can cause sudden death

Question 14

What is panitumumabs MOA?

Answer 14

Fully humanized EGFR inhibitor

Question 15

What is erlotinib and Lapatinibs MOA?

Answer 15

Inhibits INTRAcellular tyrosine kinase domain on EGFR

Question 16

How is erlotinib and Lapatinib metabolized?

Answer 16

CYP3A4

Question 17

What is an important note on Neratinib?

Answer 17

Its an irreversible HER2/EGFR inhibitor

Question 18

What type of receptor is HER 1 and 2?

Answer 18

EGFR- Epidermanl Growth Factor Receptor

Question 19

What are the HER 2 receptor inhibitors?

Answer 19

Trastuzumad and pertuzumab

Question 20

What is Trastuzumabs MOA?

Answer 20

Humanized mAb, binds to domain IV on HER2 receptor, inhibiting signal transduction, also flags for cytotoxicity

Question 21

What is the main ADE for trastuzumab and pertuzumab?

Answer 21

Cardiotoxicity

Question 22

What is pertuzumabs MOA?

Answer 22

Humanized mAb, binds to domain II on HER2 receptor, inhibiting signal transduction, also flags for cytotoxicity

Question 23

What are the two BRAF inhibitors?

Answer 23

Dabrafenib and Vemurafenib

Question 24

What are BRAF inhibitors MOA?

Answer 24

Inhibit BRAF, which can be a constitutively active kinase pathway/component

Question 25

What is the MEK inhibitor?

Answer 25

Trametinib, does what it sounds like | MEK is a downstream enzyme in the TK process

Question 26

What is the VEGF inhibitor?

Answer 26

Bevacizumab and Ziv-alfibercept

Question 27

What is VEGF?

Answer 27

Its one of the most important factors for angiogenic growth factors. Tumors secrete this to help growing.

Question 28

What is bevacizumabs MOA?

Answer 28

Prevents VEGF from binding to the receptor

Question 29

What is bevacizumabs ADE?

Answer 29

Hypertension

Question 30

What is Ziv-afilbercepts MOA?

Answer 30

Creates a decoy receptor

Question 31

What is Ziv-Afilbercepts ADEs?

Answer 31

Hypertension

Question 32

What is bortezomibs MOA?

Answer 32

Inhibits proteasomes leading to excess protein in the cell and apoptosis

Question 33

What are the mTOR inhibitors?

Answer 33

Everolimus, Temsirolimus

Question 34

What do mutations in mTOR pathway result in?

Answer 34

Exaggerate signaling and enhanced cancer cell survival

Question 35

What is everolimus active metabolite?

Answer 35

Sirolimus

Question 36

What is the MOA of Thalidomide?

Answer 36

Anti MM Activity (Multiple Myeloma) Inhibition of MM cell adhesion to bone marrow cells Decreased angiogenesis Enhanced T cell production and NK cells

Question 37

What is Thalidomide NOT ok to use in?

Answer 37

Morning Sickness. Extremely teratogenic

Question 38

What class is Rituximab?

Answer 38

Anti-CD20, basically destroys b cells (in cancer where B cells are rogue)

Question 39

What is Rituximabs ADE?

Answer 39

Chimeric, "xi", so reactions

Question 40

What is Ipilimumabs MOA?

Answer 40

Inhibits cytotoxic T lymphocyte antigen 4, so it ensures T cell activity is regained

Question 41

What is Pembrolizumads MOA?

Answer 41

Inhibits PD-1 (which is something that cancer cells use to help avoid getting destroyed by the body), so ensures programmed cell death can occur