Chemoprevention Flashcards

1
Q

What is better than a cure?

A

Prevention

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2
Q

What are some major avoidable risk factors?

A
  • Tobacco exposure
  • Diet (fibre, vitamins, meat, salt)
  • Weight/Obesity
  • Alcohol
  • Occupational exposure
  • Radiation
  • Exercise
  • Infection
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3
Q

What population study supports the importance of lifestyle and environment in the development of cancer?

A

Incidence of stomach and colorectal cancer in Japanese, Japanese living in Hawaii, and US caucasian populations

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4
Q

What is chemo/therapeutic prevention?

A

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

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5
Q

What is the most important quality in an ideal therapeutic preventative agent?

A

No (or low) toxicity

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6
Q

What else should the ideal agent be?

A
  • Highly efficacious
  • Have known mechanisms
  • Be accepted by the general population
  • Have an oral formulation, or one off vaccine
  • Cheap
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7
Q

What part of carcinogenesis provides lots of opportunity for chemoprevention?

A

Its multistep process taking many years

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8
Q

What are the two categories of chemopreventive agents?

A
  • Blocking agents

- Suppressing agents

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9
Q

What do blocking agents do?

A

Prevent carcinogens from being generated or reaching/reacting with critical target sites

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10
Q

What do suppressing agents do?

A

Act after carcinogenic exposure to suppress expression of neoplasia

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11
Q

Name some examples of targets for blocking agents

A
  • Free radical scavenging
  • antioxidant activity
  • Induction of phase 2 drug metabolising enzymes
  • Induction of DNA repair
  • Carcinogenic uptake
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12
Q

Name some targets for suppression agents

A
  • Modulation of signal transduction
  • Altering gene expression
  • Inhibition of cell proliferation
  • Induction of terminal differentiation
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13
Q

Who is primary chemo-prevention aimed at?

A
  • High-risk individuals

- Healthy subjects

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14
Q

Who is secondary chemo-prevention aimed at?

A
  • Pts with pre-invasive dysplasia

- Pts with pre-neoplastic lesions

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15
Q

Who is tertiary chemo-prevention aimed at?

A

Successfully treated cancer patients

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16
Q

How does the acceptability of toxicity change with later stages of chemo prevention?

A

It increases i.e. more risk of toxicity is tolerated for a patient who has already had cancer rather than one who hasn’t

17
Q

How does the no. patients treated to achieve significant prevention change with later stages of chemo prevention?

A

It decreases

18
Q

What is the problem with finding chemopreventative agents?

A
  • It takes decades
  • Large numbers of people are needed per study
  • It isn’t funded by pharmaceutical companies
19
Q

What would allow smaller trials and quicker assessment of efficacy?

A

Use of surrogate endpoint biomarkers

20
Q

What is the problem with some agents regarding different experimental settings?

A

An agent may inhibit carcinogenesis in one but enhance it in another

21
Q

What is the problem with patient heterogeneity in developing agents?

A

Some agents may be beneficial to some and harmful to others

22
Q

Why are dietary derived agents a good place to start?

A

Good, pre-existing evidence of safety

23
Q

Name some dietary derived chemopreventative agents

A
  • Curcumin
  • Sulforaphane
  • Resveratrol
  • EGCG
24
Q

What is resveratrol found in?

A

Red grapes and red wine

25
Q

How does tamoxifen act as a chemopreventative agent?

A

Prevents breast cancer in high risk women

26
Q

What type of cancer does tamoxifen cause a 48% decrease in?

A

Oestrogen receptor positive

27
Q

What is the probelm with tamoxifen as a chemopreventative agent?

A

Uptake is extremely low of those eligible for chemoprevention

28
Q

What serious adverse effect can tamoxifen have?

A

Increase risk of endometrial cancer and venous thromboembolic events

29
Q

What enzyme can be targeted in chemoprevention?

A

COX

30
Q

What can COX-1 and 2 be targeted by?

A

NSAIDS

31
Q

What can COX-2 be targeted by?

A

Coxibs

32
Q

What do coxibs help reduce?

A

Advanced adenomas on follow-up colonoscopy

33
Q

What adverse effects can coxibs have?

A

CVS risks

34
Q

What cheap commonplace drug can be used in chemoprevention?

A

Aspirin

35
Q

Which cancer can aspirin help prevent?

A

Colorectal cancer