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Pharmacology and Toxicology
PHAR 100
Hisham Elbatarny

Cancer Detection, Screening and Prevention; Anticancer drugs Review: Carcinogenesis is a Multistep Process Detection of Carcinogens Long-term tests in humans: • Ultimate proof • Require carefully designed epidemiological studies • Require rigorous evaluation of clinical observations Complicated because: • Humans exposed to many drugs and environmental agents • Long latent period between exposure and tumour appearance • Long and costly process • Retrospective studies Detection of Carcinoges Shorter-term tests in animals: • Officially recognized test ◦ Predictive of carcinogenic potential • Require 2 – 5 years to conduct • Costly • Results may not always be transferable ◦ High doses used, inter-species variability Ames Test • Not officially recognized • Low cost/short-term • Uses mutant bacteria that regain ability to grow when exposed to mutagenic chemicals • Good correlation between known carcinogens and +ve test results Screening for Cancer Population-Based Cancer Screening Programs Goals: • Decrease cancer death rate • Detect cancer/precancerous conditions • Improve chance of successful treatment ◦ e.g. Population screening mammography for breast cancer Prevention of Cancer • selective inhibition of carcinogen activation and enhancement of carcinogen detoxification ◦ natural and synthetic products (green tea, sulforaphane) Prevention of Cancer • antioxidants and anti-inflammatory agents ◦ beta-carotene, vitamin E and C  limited success in clinical trials ◦ non-steroidal anti-inflammatory drugs (NSAIDS)  studies show some promise in  risk of colon and breast cancer • vaccinations: e.g. Liver (Hep B and Hep C) and cervical cancer (HPV) • anti-estrogens: e.g. Tamoxifen - ↓ risk of breast cancer Prevention of Cancer *****Avoidance****** • elimination of cigarette smoking and other tobacco products • dietary restriction • moderation of alcohol intake • avoid excessive exposure to sunlight • improve exercise habits • get immunized • avoid high risk behaviour Cancer Treatment Goals: 1. Cure 2. Prolong survival 3. Relief of symptoms 4. Psychological support 5. Clinical research Treatment of Cancer Six categories of cancer treatment: 1. Surgery 2. Chemotherapy 3. Radiation 4. Biological therapies 5. Hormone therapies 6. Bone marrow transplantation Principles of Cancer Chemotherapy Benefit-risk assessment: • weighing benefits vs. adverse effects of treatment • continual evaluation General Principles: • chemotherapy often one part of overall therapy • anticancer drugs not as effective alone • anticancer drugs themselves can be carcinogens How do anticancer drugs work? • act by killing or slowing the growth of rapidly dividing cells ◦ cancer cells ◦ normal cells in bone marrow, digestive tract, hair follicles → side effects • in general, inhibit DNAsynthesis or cell division • newer agents act directly against abnormal proteins in cancer cells (targeted therapy) Complication of Cancer Chemotherapy • serious side effects limit doses ◦ bone marrow cell toxicity ◦ Anemia (↓ red blood cells)
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