43. Anti-Cancer Agents 1

Question 1

What are the 3 main approaches to eliminating cancer?

Answer 1

Surgery
Radiotherapy
Chemotherapy

Question 2

What is adjuvant therapy?

Answer 2

Systematic therapy used in patients with primary tumour removed but at risk for metastasis

Question 3

What is neoadjuvant therapy?

Answer 3

Treatment given prior to local therapy

Shrinks tumour before surgery

Question 4

What does classical chemotherapy target?

Answer 4

The cell cycle: proliferation

Question 5

What are the 4 classes of cytotoxic drugs?

Answer 5

Antimetabolites
Alkylating agents
Cytotoxic antibiotics
Plant alkaloids/microtubule inhibitors

Question 6

How do antimetabolites work?

Answer 6

Act as competitive antagonists to the metabolic pathways in the biosynthesis of DNA and RNA

Question 7

What is the most widely used folate antagonist drug?

Answer 7

Methotrexate

Question 8

What are the two types of antimetabolites?

Answer 8

Folate antagonists

Nucleic acid synthesis inhibitors

Question 9

How does methotrexate work?

Answer 9

Inhibits dihydrofolate reductase (enzyme that converts folates to tetrahydrofolate)

Question 10

How do nucleic acid synthesis inhibitors work?

Answer 10

Form false RNA/DNA which is unable/slower to replicate

Question 11

What nucleic acid synthesis inhibitor is widely used for colorectal cancer?

Answer 11

5-Fluorouracil

5-FU

Question 12

How does 5-FU work?

Answer 12

Inhibits thymidylate synthase

Incorporation of its metabolites into RNA and DNA

Question 13

What is the name of the oral version of 5-FU?

Answer 13

Capecitabine

Question 14

How do alkylating agents work?

Answer 14

Form covalent bonds with DNA
Inhibits DNA synthesis in S phase and interferes with transcription
Contains reactive alkyl groups which form covalent bonds with guanine residues

Question 15

Name 3 types of alkylating agents

Answer 15

Nitrogen mustards (cyclophosphamide)
Nitrosoureas (Carmustine)
Alkylating-like (cisplatin)

Question 16

How do cytotoxic antibiotics work?

Answer 16

Prevent cell division

Molecules lodge between DNA coils and distort shape, prevents cell replication

Question 17

Name an anthracycline

Answer 17

Doxorubicin

Question 18

How does doxorubicin work?

Answer 18

Stops uncoiling of DNA by stopping DNA-topoisomerase 2 from leaving

Question 19

What is the adverse effect of doxorubicin?

Answer 19

Cardiac toxicity
Produces O2 radicals which are normally broken down by catalase (low conc in heart) and glutathione peroxidase (inhibited by doxorubicin)

Question 20

What are the two types of plant alkaloids?

Answer 20

Vinca alkaloids

Taxanes

Question 21

How do vinca alkaloids work?

Answer 21

Spindle poison

Binds to tubulin and inhibits it polymerising into microtubules

Question 22

Name 2 vinca alkaloids

Answer 22

Vincristine

Vinblastine

Question 23

Name 2 taxanes

Answer 23

Paclitaxel

Docetaxel

Question 24

How do taxanes work?

Answer 24

Promotes formation of intracellular microtubules and prevents their dissassembly

Question 25

What ways can drug resistance manifest?

Answer 25

Decrease in amount taken up
Insufficient activation
Increased conc of target enzyme
Alternative metabolic pathways
Repair of drug induced lesion

Question 26

What is multidrug resistance?

Answer 26

Simultaneous resistance to many structurally dissimilar anticancer drugs
Development of transport proteins to pump drug out of cancer cell