Download Cancer Prevention/Chemoprevention

Biology 207
Spring 2004
Biology of Cancer
Lecture 20: Cancer Prevention/Chemoprevention
Reading: King Chapter 14
Other sources:
Cuzick, J. et al. 2003. Overview of the main outcomes in breast cancer
prevention trials. The Lancet 361: 296-300.
http://press2.nci.nih.gov/sciencebehind/estrogen/estrogen01.htm
Lecture Outline
1. Lifestyle changes to reduce risk
2. Chemoprevention
Lecture:
1. Lifestyle changes to reduce cancer risk:
Preventative action
stop smoking
reduce alcohol
protect from UV light; "wear sunscreen"
minimize exposure to X-rays
check house for radon
(less than 4 pCi/l)
don’t live next door to nuclear plants
weight less than 40% over
recommended
reduce fat
reduce smoked, pickled foods
reduce chemical exposure at work
safe sex (most tumor causing viruses
are sexually transmitted)
Reduces cancer
lung, colon etc.
liver
skin cancers, melanoma
all types
lung
nuclear accidents--leukemia
endometrial
colon, breast cancer?
stomach
varies
hepatitis B--liver;
papilloma virus--cervical, anogenital
HIV/HHV-8-- Kaposi’s sarcoma
breast cancer
minimize estrogen replacement
therapy
2. Chemoprevention: using food, drugs, vitamins or minerals to help prevent
cancer
foods: “antioxidants” vitamins C and E beta-carotene, chemicals in green tea,
turmeric (yellow spice in East Indian food)
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Act as blocking agents: Prevent potential carcinogens from being converted to
carcinogens by metabolism or prevent “oxidative damage”--formation of free
radicals that can alter DNA.
Usually vitamins obtained from diet more effective than supplements in reducing
cancer risk.
"antioxidants act as protective substances by destroying free radicals, which are
the harmful by-products formed through the body's metabolism. Free
radicals damage cells and initiate carcinogenesis.. . .Studies have shown that
antioxidants work best when combined and that the presence of fiber and other
plant compounds may provide additional health benefits. Consequently it is
recommended that you get most of your antioxidants from your diet rather than
relying on supplements. Although toxic levels for antioxidants have not been
established, excessive levels can be harmful and may interfere with cancer
therapies." Katrina Claghorn, RD, Oncology Dietitian for The University of
Pennsylvania Health System, Oncolink web site
Suppressing agents: vitamin A, calcium, tamoxifen
Prevent cell proliferation. Vit. A shown to prevent head/neck cancers.
substances in broccoli and cruciferous vegetables (dithiolthiones and others)-inhibit growth of tumors in rats; activates liver detoxification enzymes.
soy (genistein)--reduces mammary tumors in rats, inhibits angiogenesis, early
testing for chemoprevention of colon cancer.
Tamoxifen: Blocks action of estrogen; for chemoprevention of breast cancer in
women at high risk.
Tamoxifen study: view on-line tutorial
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Structure/function of estrogen
How estrogen controls growth
Tamoxifen acts as anti-estrogen
Clinical trials of tamoxifen
 US study of ~37,000 women, estrogen receptor positive/negative
 Reduce breast cancer in women at high risk
 ER positive cases: get greatest reduction
 Tamoxifen has some risk (endometrial cancer, blot clots)
 Raloxifen in trials
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drugs in testing as chemotherapeutic agents:
DFMO--difluoromethylornithine: Inhibits enzyme essential for cell proliferation.
NSAIDS--non-steriod anti-inflammatory drugs.
 These inhibit prostaglandin synthesis and release.
 Drugs like aspirin and ibuprofen are non-specific inhibitors and work on
both COX-1 and COX-2 enzymes, thus act as anti-inflammatory drugs, but
can irritate the stomach.
 New "COX-2 inhibitors" like Celebrex approved for arthritis, are more
specific for inflammation.
 COX-2 inhibitors are proving effective in prevention of reoccurring colon
cancer and are being tested for lung and other cancers.
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