Breast (Most overall) > Lung > Colorectal > Ovarian
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Trend of cancer? (1)
incidence is increasing. Incidence and mortality are diverging.
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Top three cancers with highest survival rates? (3)
Testicular, Malignant melanoma, Hodgkins lymphoma
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Reasons for failure of classical chemotherapies? (3)
Toxicity to normal tissue (NTI), Life threatening, Emergence of Resistance.
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Types of toxicity? (5)
Myelosuppression (Anaemia, Nuetropenia, Thrombocytopenia, Pancytopenia), GI, Skin and hair.
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GI toxicity is managed with? (2)
5-HT antagonists Ondansetron and Granisetron
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Which chemotherapies cause worst hair damage? (2)
Doxorubicin and Etoposide
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How is this helped? (1)
Cold Cap
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3 types of chemo resistance? (3)
Apparent - inadequate drug delivery. Inherent - cells dont have biochemical machinery to respond. Acquired - initially responsive over time resistant cells form; specific or all drugs.
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Pancreatic cancer; life expectancy? (1)
6 month avg.
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What is each phase of clinical trails for? (3)
Phase I - MTD and type of toxicity. Phase II - Disease specific activity. Phase III - New drug v existing therapies
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Approaches to new drug development? (3)
Random drug screening. Target orientated development. Phenotype based development.
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Random drug screening is done by?
National Cancer Institute
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How many cell lines are tested?
60
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Define GI50, TGI and LC50. (3)
GI50 - Conc. needed for 50% growth inhibition. TGI - total (100%) growth inhibition. LC50 - Lethal conc. kills 50% of cells.
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Selection criteria for further development?
Disease Severity, COMPARE - compare fingerprint/MoA identifies new MoA, Molecular target - response compared to expression of target
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Explain false -ve predictions using an example?
Cyclophosphamide. Pro-drug metabolised by CYP. No action in vitro as enzymes not present.
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Hanahan and Weinberg (2000) Hallmarks of cancer? (6)
Sustaining proliferative signalling. Evading growth suppressors. Active invasion and metastasis. Enabling replicative immortality. Inducing angiogenesis. Resisting cell death.
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