Anti-Cancer drugs

Question 1

Cancer

Answer 1

Cancer is a disease of DNA

Carcinogens and inheritance of certain genes can lead to the development of cancer and hence a tumour

Question 2

Replication checkpoints

Answer 2

Mitotic cell division has several checkpoints that help to prevent the replication of potentially cancerous cells

G1 phase = at the end of G1 phase, any damaged DNA is detected

S phase = in the middle of S phase, any unreplicated or damaged DNA is detected

G2 phase = at the end of G2 phase, any unreplicated or damaged DNA is detected

M phase = during M phase, chromosome misalignment is detected

Question 3

Extrinsic apoptosis pathway

Answer 3

Extrinsic compounds bind to death receptors (CD95)

This triggers pro-caspase which activates the caspase cascade

Question 4

Intrinsic apoptosis pathway

Answer 4

DNA damage results in the phosphorylation of p53

This releases bax, bad and bid which punch holes in the mitochondrial membrane

This allows leakage of cytochrome C, triggering the caspase cascade

Question 5

Chemotherapy

Answer 5

Chemotherapy can impact many points in the cell cycle

• DNA damaging agents
• Anti-metabolites
• Cytotoxic antibiotics
• Plant derivatives

Question 6

Alkylating agents

Answer 6

DNA damaging agents

Form covalent bonds within the DNA, impeding replication

N7 & O6 of adjacent guanines become crosslinked

There are several types:

• Platinum-based alkylating agents
• Nitrogen mustard alkylating agents
• Nitrosoureas alkylating agents

Question 7

Folate antagonists

Answer 7

Anti-metabolites

Competitively inhibit dihydrofolate reductase, preventing purine synthesis

Can be overcome if dietary intake of folate is high

Question 8

Purine analogues

Answer 8

Anti-metabolites

Inhibit thymidylate synthetase, thereby inhibiting the folate pathway and inhibiting DNA synthesis

Question 9

Purine deaminase inhibitors

Answer 9

Anti-metabolites

Inhibit adenosine deaminase to prevent purine degradation

Means that the bases are not recycled, so DNA synthesis is prevented

Question 10

Pyrimidine analogues

Answer 10

Anti-metabolites

Bind to DNA polymerase, inhibiting its action

Question 11

Anthracyclines

Answer 11

Cytotoxic antibiotics

Inhibitor of topoisomerase II & DNA/RNA polymerases

Prevents replication

Question 12

Vinca alkaloids

Answer 12

Plant derivatives - from the periwinkle plant

Bind to tubulin, preventing spindle formation and causing the cell cycle to arrest in metaphase

Question 13

Taxanes

Answer 13

Plant derivatives - from the bark of the Pacific Yew tree

Inhibit tubulin to prevent microtubule assembly

Prevents cytokinesis

Question 14

Topoisomerase inhibitors

Answer 14

Plant derivatives - from the mandrake plant

Binds to the complex formed between DNA and topoisomerase,causing rigidity, leading to double-stranded DNA breaks