Cancer and Chemotherapy

Question 1

What are adjuvants and neoadjuvants?

Answer 1

Neoadjuvants are given before surgery to shrink the tumour.

Adjuvants are given after surgery to destroy the remaining cells and prevent recurrence.

Question 2

What are the 6 principles governing use of cancer chemo?

Answer 2

1. Specificity of drugs
2. Kinetics of tumour growth and detection
3. Drug efficacy and fixed proportional killing
4. Drug efficacy and tumour regrowth.
5. Cell cycle susceptibility to drug
6. Drug resistance

Question 3

Describe the impact of specificity of cancer drugs on normal human cells.

Answer 3

Cancer drugs target highly proliferative cells.

As well as tumour cells, they also poison GI tract cells, hair follicles and bone marrow / haematopoietic cells.

This results in GI toxicity, hair loss and myelosuppression.

Question 4

What is the role of the cell cycle in chemo effectiveness?

Answer 4

Many cancer drugs target dividing cells, and thus cells in G0 can be resistant.

Different drugs act at different stages of the cell cycle, and thus drug combinations are effective.

Question 5

Give an example of phases specific (4) drugs.

Answer 5

S phase dependent: Anti-metabolites

M-phase dependent: Vinka alkaloids

G1-phase dependent: Corticosteroids

G2-phase depedent: Antibiotics

Question 6

Describe the action of alkylating agents, and give a few examples.

Answer 6

Alkylating agents form DNA adducts, damaging DNA and thus preventing replication.

It kills cells, irrespective of cell cycle stage.

Examples:
Nitrogen mustard: Cyclophosphamide
Alkyl-sulphonates: Busulphan

Question 7

Describe the action of anti-metabolites and give two sub classes and an example from each.

Answer 7

Anti metabolites deprive cells of building blocks required for growth.

Folic acid antagonists: Methotrexate

DNA base analogues: Mercaptopurine

Question 8

Describe the action of mitotic inhibitors and give two examples.

Answer 8

Interfere with mitotic spindle.

Vinka alkaloids prevent mitotic spindle formation.

Taxanes (e.g. Paclitaxel) block the use of already formed spindle.

Question 9

Describe the action of antibiotics in treating cancer and give two examples.

Answer 9

Naturally derived, attack tumour cells.

Anthracyclines - intercalate between base pairs. Cardiotoxic.

Bleomycins - produce free radicals that damage DNA. Cause pulmonary fibrosis.

Question 10

What is tamoxifen?

Answer 10

Hormone used to treat breast cancer.

Question 11

What are anti-androgens used for?

Answer 11

Treat prostate cancer.

Question 12

What is the specific organ related side effect of methotrexate?

Answer 12

Hepatotoxicity.

Question 13

How does radiotherapy work?

Answer 13

Radiotherapy ionises water, creating free radicals that damage DNA, leading to apoptosis.

Question 14

What are the 8 capabilities of cancer cells?

Answer 14

1. Self-sufficient growth signals
2. Insensitive to anti-growth signals
3. Evade apoptosis
4. Proliferate indefinitely
5. Angiogenesis
6. Invasion and metastasis
7. Cellular energy deregulation
8. Immune system evasion

Question 15

Describe how tumour cells become self-sufficient in growth signals.

Answer 15

Cells are quiescent (G0) without growth signals.

Cancer cells have oncogene activation, and produce their own.

Question 16

What is the major factor in insensitivity to anti-growth signals.

Answer 16

Tumour suppressors (E.g. Retinoblastoma) are mutated.

Question 17

How do tumour cells achieve indefinite proliferation?

Answer 17

Overactivity of telomerase/

Question 18

What are the positive and negative signals for angiogenesis.

Answer 18

Positive - VEGF

Negative - Tsp-1