Cancer Chemotherapy

Question 1

List the special characteristics of cancer cells

Answer 1

• uncontrolled proliferation
• loss of original function (anaplasia)
• Invasiveness
• metastasis (malignant cells)

Question 2

What are the different molecular changes that can occur to transform a cell into a cancer cell?

Answer 2

• DNA change
• either inactivation of TSG or activation of proto-oncogenes into oncogenes
• regulatory genes become muted

Question 3

What are the anti-cancer defences of the body?

Answer 3

• immune system
• apoptosis

Question 4

What do anti-cancer drugs target?

Answer 4

Cell division

Question 5

List the toxic effects of anti-cancer drugs

Answer 5

• bone marrow suppression (anaemia, immune depression, impaired wound healing)
• hairloss
• damage to GI epithelium
• liver, heart, kidney damage
• depression of growth in children
• sterility
• teratogenicity

Question 6

Describe the cell division cycle

Answer 6

• S-phase: DNA replication (chromosomal replication)
• GAP-2
• nuclear division (mitosis), cytokinesis and separation of chromosomes into daughter cells
• G0 (rest phase)
• G1 = mature cell development until ready for next division
• restriction point = cell is checked (if fails = apoptosis)

Question 7

Why must anti-cancer drugs be administered multiple times and in cycles?

Answer 7

Because not all cells in the cancer cell population are dividing at one specific time and therefore only a sub-population of the cells are targeted

Question 8

What are the different types of cancer chemotherapy?

Answer 8

• cell-cycle specific drugs = drugs only active on dividing cells
• cell-cycle non-specific drugs = drugs active on resting phase (G) cells as well

Question 9

What do solid tumours consist of?

Answer 9

• dividing cells (sensitive to cell-cycle specific drugs)
• resting cells (not dividing but can do - can cause relapse)
• cells which can no longer divide but contribute to tumour size (unproblematic)

Question 10

What are the broad classes of chemotherapy drugs?

Answer 10

• alkylating agents
• anti-metabolites
• cytotoxic antibiotics
• microtubule inhibitors
• steroid hormones

Question 11

What is the mechanism of action of alkylating agents and give an example?

Answer 11

• contain 2 reactive groups which form strong covalent bonds with DNA
• cross-links to prevent the separation of DNA strands in replication
• interference of transcription and replication of DNA
• eg. Nitrogen mustards - cyclophosphamide

Question 12

Describe the mechanism of action of anti-metabolites

Answer 12

Interferes with nucleotide/DNA synthesis

Question 13

Describe the mechanism of action of cytotoxic antibiotics

Answer 13

Act directly on DNA as intercalators

Question 14

Describe the mechanism of action of microtubule inhibitors

Answer 14

Bind to microtubule protein which blocks polymerisation and normal spindle formation so that cells cannot divide

Question 15

Describe the mechanism of action of steroid hormones

Answer 15

• more specific
• targets hormones which regulate physiological functions of tumours

Question 16

Describe how different anti-metabolites prevent nucleotide synthesis

Answer 16

• methotrexate: inhibit dihydrofolate in folate cycle associated with thymidine synthesis
• 5FU: prevents thymidine formation
• cytarabine: causes DNA chain termination by disruption due to presence of ribose instead of cytidine
• mercaptopurine: causes conversion of nucleotides into false ones which disrupts purine nucleotide synthesis and the double helix

Question 17

Describe how different cytotoxic antibiotics prevents cell division

Answer 17

• dactinomycin: inserts itself and binds into minor groove in DNA helix disrupting RNA polymerase induced separation of strands
• doxorubicin: inserts itself between base pairings causing local uncoiling and prevention of continuous separation of DNA strands
• both come from the streptomyces family of bacteria

Question 18

Describe how different steroid hormones prevent cell division

Answer 18

• prednisone: synthetic adrenocorticoid hormone (converted to active form in body)
• prednisolone: suppresses lymphocyte growth
• tamoxifen: oestrogen receptor antagonist
• Flutamide: testosterone receptor antagonist