11) Chemoprevention

Question 1

What is chemo/therapeutic prevention?

Answer 1

Use of natural or synthetic compounds to reverse, suppress, prevent or delay carcinogenic progression to invasive cancer

Question 2

What are the features of the ideal preventative agent?

Answer 2

High efficacy 
No toxicity 
Known mechanism 
Oral 
Low cost

Question 3

What is primary prevention?

Answer 3

Prevention in healthy subjects or high risk individuals

Question 4

What is secondary prevention?

Answer 4

Screening looking for pre-malignant lesions

Question 5

What is tertiary prevention?

Answer 5

Preventing relapse in those who have been sucessfully treated

Question 6

How does lifestyle play a role in the development of neoplasia?

Answer 6

Avoidable risk factors account for 43% of all new cases of cancer e.g. smoking, diet, alcohol

Question 7

What are the WCRF/AICR lifestyle recommendations?

Answer 7

Be as lean as possible 
Physically active for 30 mins 
Avoid sugary drinks and fatty food 
Eat more fruit and veg
Limit red and processed meats
Limit salt
Limit alcohol
Don't use supplements to protect against cancer

Question 8

What are cancer blocking agents?

Answer 8

Compounds which inhibit carcinogenesis by preventing carcinogens from being generated or reaching tissue and causing DNA damage

Question 9

What are cancer suppressing agents?

Answer 9

Compounds which act after carcinogenic exposure by suppressing the expression of neoplasia

Question 10

What mechanisms do cancer blocking agents use?

Answer 10

Scavenging free radicals
Induction of DNA repair
Blocking carcinogen uptake

Question 11

What are some mechanisms that suppressing agents use?

Answer 11

Alteration of gene expression
Inhibition of cell proliferation
induction of apoptosis
Modulation of signal transduction

Question 12

What are some challenges to trials into chemoprevention?

Answer 12

Long follow up time
Need a large sample size
Difficult to get funding

Question 13

How can genetic polymorphisms affect

individual response to treatment?

Answer 13

Differences in drug metabolising enzymes, repair enzymes and cell signalling molecules

Question 14

What are the features of dietary derived preventative agents?

Answer 14

Pre-existing evidence of safety
Regularly consumed in diet
Multi-targeted

Question 15

What are surrogate endpoint biomarkers?

Answer 15

Outcomes other than cancer that give an indication of whether the drug is working early

Question 16

Describe the agent development process:

Answer 16

In vitro models -> efficacy in rodent models -> pilot studies in healthy volunteers -> clinical efficacy

Question 17

How can chemopreventive efficacy be assessed?

Answer 17

Decreased number of cancer cells
Induction of apoptosis
Modulation of signalling

Question 18

How are rodent models used in chemoprevention?

Answer 18

Genetically engineered rodents with mutated genes that initiate cancer, can then test with these

Question 19

What is the mechanism of action of tamoxifen?

Answer 19

Selective oestrogen recepetor modulator - anti-oestrogen at breast

Question 20

How can tamoxifen be used in chemoprevention?

Answer 20

Decreases growth of human breast cancer cells
Decrease in new tumours on contralateral breast
Prevent breast cancer in high risk women

Question 21

What are the serious side effects of tamoxifen?

Answer 21

Endometrial cancer

Venous thromboembolic events

Question 22

What are the problems with coxibs as chemopreventive agents?

Answer 22

Cardiovascular risks

Question 23

How can aspirin be used in chemoprevention?

Answer 23

Reduces risk of colorectal carcinoma and deaths associated with CRC
Can be used in patients with Lynch syndrome

Question 24

Is beta-carotene a chemopreventive agent?

Answer 24

No, studies show that it increased risk of lung cancer - may be due to high dose