Pharmacology - Antineoplastic Drugs (Exam 5)

Question 1

MOA of alkylating agents

Answer 1

1. Nucleophilic substitution to form a cyclic sulfonium ion
2. This very reactive intermediate tends to cause permanent alkylation of the guanine nucleotide in DNA strands
3. This can prevent cellular division and lead to programmed cell death (Apoptosis) because of the DNA Damage response (DDR).

Question 2

MOA of anti-metabolites

Answer 2

inhibits DNA, RNA, protein synthesis

May also interfere with cellular metabolism and inhibit mitosis

Question 3

MOA of antibiotics

Answer 3

Intercalates with DNA causing topisomerase stalling

Question 4

MOA of vinca alkaloids

Answer 4

Bind tubulin and prevent microtubule polymerization

Question 5

How does the mechanism of platinum drugs induce DNA damage?

Answer 5

Covalent binding to DNA -> inhibits DNA replication -> cell cycle gets arrested -> cessation of cancer cell proliferation

Question 6

How does the mechanism of campothecin drugs induce DNA damage?

Answer 6

Target TOPO I -> interferes with DNA replication -> DNA damage

Question 7

How does the mechanism of podophyllotoxins induce DNA damage?

Answer 7

Targets TOPO II

Question 8

The goal of _______________ is to eradicate every viable tumor cell without significantly damaging normal host tissue.

Answer 8

chemotherapy

Question 9

Cell division requires 2 things. What are they?

Answer 9

1) coordinated microtubules
2) DNA synthesis

Question 10

Name 2 microtubule modulating agents

Answer 10

taxanes and epothilones

Question 11

Name one etoposide that works by targeting TOPO II

Answer 11

podophyllotoxin

Question 12

Mechanism of action of anti-folates

Answer 12

block thymidylate synthesis aka purine synthesis

Question 13

How does taxane induce cell cycle arrest?

Answer 13

binds tubulin and prevents microtubule depolymerization -> this prevents formation of the mitotic spindle so cells are arrested in the M phase

Question 14

How does epothilones induce cell cycle arrest?

Answer 14

inhibit microtubule function

Question 15

A platinum based drug that binds to DNA and inhibits replication

Answer 15

cisplatin

Question 16

Dental implications of anthracyclins

Answer 16

-soreness of the mouth
-mouth ulcers
-mucositis

Question 17

Examples of differentiating agents

Answer 17

retinoic acid (there are others but he said focus on this)

Question 18

Bisphosphonates modulate?

Answer 18

Bone metabolism

Question 19

Dental implication of bisphosphonates

Answer 19

Osteonecrosis of the jaw (mandible more than maxilla)

Question 20

T/F: Chemotherapy only acts directly on the DNA of the cell

Answer 20

False! it’s direct OR indirect

Question 21

Difference b/w chemotherapy and targeted therapy

Answer 21

Chemo: non-specific toxicity (less effective, more side effects)
Targeted: hit tumor specific characteristics (more effective, less toxic)

Question 22

Name a hormone agonist and antagonist

Answer 22

agonist: prednisone
antagonist: tamoxifen

Question 23

MOA of hormone agonist (prednisone)

Answer 23

Binds glucocorticoid receptors to suppress inflammation

Question 24

MOA of hormone antagonist (tamoxifen)

Answer 24

Binds estrogen receptor and blocks its interaction with estrogen

Question 25

T/F: Signal transduction pathways are linear.

Answer 25

False!! They’re super complicated and have many negative feedback loops

Question 26

What are small molecule drugs for targeted therapy called?

Answer 26

Magic bullets

Question 27

Dental toxicities reported with tamoxifen

Answer 27

Increases in gingival inflammation, gingival bleeding, xerostomia, and burning sensations in oral tissues.

Occasional reports of dental caries.

Question 28

Tamoxifen binds and inhibits…

Answer 28

Protein Kinase C
Calmodulin
P glycoproteins
Ca channels

Question 29

The poster child for targeted therapies

Answer 29

BCR-ABL CML

Question 30

MOA of BCR-ABL

Answer 30

ABL is a kinase.

The fusion with BCR serves to activate the kinase without control

Leads to hyperactive signaling pathways and cancer development.

Question 31

Penicillin for some cancers

Answer 31

Gleevec/Imatininb

Question 32

Gleevec/Imatinib is designed to hit?

Answer 32

BCR-ABL

Question 33

MOA of ALK inhibitors

Answer 33

Competitive binder for the ATP pocket, like Gleevec

Question 34

About 50% of melanomas have ________ mutations

Answer 34

B-Raf

Question 35

Mek-1 inhibitors work with _________ in melanoma

Answer 35

B-Raf inhibitors

Question 36

MOA of Ras inhibitors

Answer 36

Covalently binds to cysteine reside of Kras 12C

Question 37

Aromatase inhibitors may be associated with elevated

Answer 37

Periodontitis

Question 38

Rapalogs toxicity

Answer 38

Stomatitis, rash, anemia

Question 39

Example of antibody targeted therapy

Answer 39

Rituximab

Question 40

Antibody against HER2/Neu for treating breast cancer

Answer 40

Herceptin

Question 41

Antibody that blocks activation and promotes EGFR degradation

Answer 41

Anti-EGFR

Question 42

Checkpoint protein on immune cells called T cells. It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body

Answer 42

PD-1

Question 43

Why is combination immune checkpoint therapy the most effective? (ON EXAM)

Answer 43

1.To attempt to gain additive or synergistic anti-tumor effects.
2.To overcome the tendency for tumors to develop resistance.
3.Combinations can enhance toxicity.

Question 44

Immunotherapy toxicity in oral cavity

Answer 44

Lichen planus
Stevens-johnson syndrome
Sjogren syndrome (basically extreme xerostomia)

Question 45

Name some targeted therapies for treating cancer (6)

Answer 45

1. Hormone agonists and antagonists
2. Monoclonal antibodies
3. Kinase inhibitors
4. RAS inhibitors
5. Angiogenesis inhibitors
6. Immune checkpoint inhibitors