Chemoprevention Flashcards
What is better than a cure?
Prevention
What are some major avoidable risk factors?
- Tobacco exposure
- Diet (fibre, vitamins, meat, salt)
- Weight/Obesity
- Alcohol
- Occupational exposure
- Radiation
- Exercise
- Infection
What population study supports the importance of lifestyle and environment in the development of cancer?
Incidence of stomach and colorectal cancer in Japanese, Japanese living in Hawaii, and US caucasian populations
What is chemo/therapeutic prevention?
Use of natural or synthetic compounds to reverse, suppress or delay carcinogenic progression to invasive cancer
What is the most important quality in an ideal therapeutic preventative agent?
No (or low) toxicity
What else should the ideal agent be?
- Highly efficacious
- Have known mechanisms
- Be accepted by the general population
- Have an oral formulation, or one off vaccine
- Cheap
What part of carcinogenesis provides lots of opportunity for chemoprevention?
Its multistep process taking many years
What are the two categories of chemopreventive agents?
- Blocking agents
- Suppressing agents
What do blocking agents do?
Prevent carcinogens from being generated or reaching/reacting with critical target sites
What do suppressing agents do?
Act after carcinogenic exposure to suppress expression of neoplasia
Name some examples of targets for blocking agents
- Free radical scavenging
- antioxidant activity
- Induction of phase 2 drug metabolising enzymes
- Induction of DNA repair
- Carcinogenic uptake
Name some targets for suppression agents
- Modulation of signal transduction
- Altering gene expression
- Inhibition of cell proliferation
- Induction of terminal differentiation
Who is primary chemo-prevention aimed at?
- High-risk individuals
- Healthy subjects
Who is secondary chemo-prevention aimed at?
- Pts with pre-invasive dysplasia
- Pts with pre-neoplastic lesions
Who is tertiary chemo-prevention aimed at?
Successfully treated cancer patients
How does the acceptability of toxicity change with later stages of chemo prevention?
It increases i.e. more risk of toxicity is tolerated for a patient who has already had cancer rather than one who hasn’t
How does the no. patients treated to achieve significant prevention change with later stages of chemo prevention?
It decreases
What is the problem with finding chemopreventative agents?
- It takes decades
- Large numbers of people are needed per study
- It isn’t funded by pharmaceutical companies
What would allow smaller trials and quicker assessment of efficacy?
Use of surrogate endpoint biomarkers
What is the problem with some agents regarding different experimental settings?
An agent may inhibit carcinogenesis in one but enhance it in another
What is the problem with patient heterogeneity in developing agents?
Some agents may be beneficial to some and harmful to others
Why are dietary derived agents a good place to start?
Good, pre-existing evidence of safety
Name some dietary derived chemopreventative agents
- Curcumin
- Sulforaphane
- Resveratrol
- EGCG
What is resveratrol found in?
Red grapes and red wine
How does tamoxifen act as a chemopreventative agent?
Prevents breast cancer in high risk women
What type of cancer does tamoxifen cause a 48% decrease in?
Oestrogen receptor positive
What is the probelm with tamoxifen as a chemopreventative agent?
Uptake is extremely low of those eligible for chemoprevention
What serious adverse effect can tamoxifen have?
Increase risk of endometrial cancer and venous thromboembolic events
What enzyme can be targeted in chemoprevention?
COX
What can COX-1 and 2 be targeted by?
NSAIDS
What can COX-2 be targeted by?
Coxibs
What do coxibs help reduce?
Advanced adenomas on follow-up colonoscopy
What adverse effects can coxibs have?
CVS risks
What cheap commonplace drug can be used in chemoprevention?
Aspirin
Which cancer can aspirin help prevent?
Colorectal cancer
