Molecular Targets of Cancer Pt. 2

Question 1

Cancer can develop resistance to chemotherapy via the following mechanism(s). (select all that apply).
By Upregulating apoptosis
By downregulating target enzymes
By downregulating enzymes essential for drug transport
By inhibiting enzymes involved in inactivating biotransformation

Answer 1

By downregulating target enzymes
By downregulating enzymes essential for drug transport
By inhibiting enzymes involved in inactivating biotransformation (SOMETIMES)

Question 2

List the purine nucleotides

Answer 2

Adenine and Guanine

Question 3

List the pyrimidine nucleotides

Answer 3

Cytosine, Thymine and Uracil

Question 4

What is responsible for reducing all ribonucleotides to deoxyribonucleotides?

Answer 4

Ribonucleotide reductase

Question 5

True or false: 5-Fluorouracil induces DNA synthesis by upregulating biosynthesis of thymidylate

Answer 5

False. 5-FU inhibits DNA synthesis by interfering with the biosynthesis of thymidylate

Question 6

How does 5-FU exhibit toxicity?

Answer 6

It depletes thymidylate from cancer cells as well as normal cells

Question 7

6-Mercaptopurine (6-MP), azathioprine (AZA) and thioguanine are structural analogues of what?

Answer 7

Purines

Question 8

True or false: AZA is a prodrug form of 6-MP

Answer 8

True

Question 9

What is the major clinical application of 6-MP?

Answer 9

Acute Lymphoblastic Leukemia (ALL)

Question 10

Hydroxyurea MOA

Answer 10

Inhibits ribonucleotide reductase

Question 11

Adverse effect of hydroxyurea

Answer 11

Long term use can actually cause cancer (leukemogenic)

Question 12

DNA alkylators (induce/inhibit) mutagenesis and (induce/inhibit) carcinogenesis

Answer 12

Induce, induce

Question 13

True or false: Some organometallic agents damage DNA via interstrand cross-linking

Answer 13

True

Question 14

Describe the mechanism of resistance

Answer 14

Highly reactive drugs can be deactivated by intracellular nucleophiles, like glutathione

Question 15

Cisplatin use and MOA

Answer 15

Most active drug in treating testicular cancer. Targets nucleophilic centers in guanine, adenine and cytosine

Question 16

Which conformation of cisplatin exhibits greater antitumor activity?

Answer 16

Cis conformation

Question 17

True or false: The trans conformation of cisplatin binds covalently to DNA

Answer 17

True

Question 18

Bleomycin MOA

Answer 18

Binds DNA and chelates iron(II), forming free radicals which cause single and double stranded DNA breaks

Question 19

List examples of taxanes and their MOA

Answer 19

Paclitaxel, docetaxel, cabazitaxel; inhibit microtubule depolymerization

Question 20

True or false: The presence of the two chloride leaving groups on Cyclophosphamide allows the alkylating agent to cross-link proteins

Answer 20

False

Question 21

Long term use of this ribonucleotide reductase inhibitor may be leukemogenic.

a) Gemcitabine
b) Hydroxyurea
c) Cyclophosphamide
d) Carboplatin

Answer 21

Hydroxyurea

Question 22

True or false: EGF receptor agonists are a class of drugs used in the to block a pathway that drives cancer growth

Answer 22

False. EGF receptor antagonists

Question 23

Adverse effects of EGFR antagonists

Answer 23

Skin rash and diarrhea

Question 24

Oncogenic mutation of ____ is found in approximately 30% of human cancers

Answer 24

Ras

Question 25

True or false: Solid tumors require development of a neovasculature in order to sustain growth and survive conditions of hypoxia

Answer 25

True