11) Chemoprevention Flashcards
What is chemo/therapeutic prevention?
Use of natural or synthetic compounds to reverse, suppress, prevent or delay carcinogenic progression to invasive cancer
What are the features of the ideal preventative agent?
High efficacy No toxicity Known mechanism Oral Low cost
What is primary prevention?
Prevention in healthy subjects or high risk individuals
What is secondary prevention?
Screening looking for pre-malignant lesions
What is tertiary prevention?
Preventing relapse in those who have been sucessfully treated
How does lifestyle play a role in the development of neoplasia?
Avoidable risk factors account for 43% of all new cases of cancer e.g. smoking, diet, alcohol
What are the WCRF/AICR lifestyle recommendations?
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
What are cancer blocking agents?
Compounds which inhibit carcinogenesis by preventing carcinogens from being generated or reaching tissue and causing DNA damage
What are cancer suppressing agents?
Compounds which act after carcinogenic exposure by suppressing the expression of neoplasia
What mechanisms do cancer blocking agents use?
Scavenging free radicals
Induction of DNA repair
Blocking carcinogen uptake
What are some mechanisms that suppressing agents use?
Alteration of gene expression
Inhibition of cell proliferation
induction of apoptosis
Modulation of signal transduction
What are some challenges to trials into chemoprevention?
Long follow up time
Need a large sample size
Difficult to get funding
How can genetic polymorphisms affect
individual response to treatment?
Differences in drug metabolising enzymes, repair enzymes and cell signalling molecules
What are the features of dietary derived preventative agents?
Pre-existing evidence of safety
Regularly consumed in diet
Multi-targeted
What are surrogate endpoint biomarkers?
Outcomes other than cancer that give an indication of whether the drug is working early
Describe the agent development process:
In vitro models -> efficacy in rodent models -> pilot studies in healthy volunteers -> clinical efficacy
How can chemopreventive efficacy be assessed?
Decreased number of cancer cells
Induction of apoptosis
Modulation of signalling
How are rodent models used in chemoprevention?
Genetically engineered rodents with mutated genes that initiate cancer, can then test with these
What is the mechanism of action of tamoxifen?
Selective oestrogen recepetor modulator - anti-oestrogen at breast
How can tamoxifen be used in chemoprevention?
Decreases growth of human breast cancer cells
Decrease in new tumours on contralateral breast
Prevent breast cancer in high risk women
What are the serious side effects of tamoxifen?
Endometrial cancer
Venous thromboembolic events
What are the problems with coxibs as chemopreventive agents?
Cardiovascular risks
How can aspirin be used in chemoprevention?
Reduces risk of colorectal carcinoma and deaths associated with CRC
Can be used in patients with Lynch syndrome
Is beta-carotene a chemopreventive agent?
No, studies show that it increased risk of lung cancer - may be due to high dose
