PCL102H1 Study Guide - Midterm Guide: Chemical Space, Ovulation, Prodrug
8 Jun 2018
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PCL102H 2013
PCL102H1 Spring 2013 THE ART OF DRUG DISCOVERY
Lecture 9: Mechanisms of Disease – Cancer
Hallmarks of Cancer
1. Growth signal autonomy (overgrowth)
2. Ignoring stop signals (ignoring tumor suppressor genes)
3. Evasion of apoptosis (avoiding cell suicide)
4. Angiogenesis (attracting blood vessels into tumor to deliver nutrients and carry
away waste)
5. Unlimited replicative potential (telomere elongation)
6. Metastasis (invading other parts of the body)
cancer cells avoid detection by B cells and T cells → adjuvant therapy: stimulating the
immune system to make them hypersensitive
cancer often arises from mutations
pathology: the study of diseases
Chronic Myloid Leukemia (CML)
caused by the Philadelphia chromosome
mutated B-RAF protein causes overgrowth
the action of the protein can be blocked by Gleevec
tumor-specific screening for phase I trials
CML with certain mutations are Gleevec resistant because Gleevec can't bind to them
Lung Cancer
EGFR (growth factor receptor) triggers cell growth and division when ATP binds to it
Iressa binds to EGFR by competitive inhibition
Cancer is a genetic disease because it is caused by DNA mutations by chemicals, viruses/bacteria,
or radiation. Most cancer mutations occur in soma cells.
Mechanisms of Disease: Cancer
1/3 incidences → 1/4 deaths
malignant vs. benign tumors (only malignant can metastasize)
a cytotoxic (cell-killing) approach kills fast growing cells including, but not limited to
cancer cells → this explains the side effects of chemotherapy
20-year lag time between smoking and lung cancer
Proto-oncogenes → oncogenes (pedal)
Tumor suppressor genes (brake)
pathology screening
cervical cancer screening
microscopic appearance of cancer cells
molecular screens
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Distribution of these notes are permitted as long as no alterations are made.
find more resources at oneclass.com
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PCL102H 2013
biopsy
Current challenges of discovering cancer treating drugs:
targeted therapy (we want a wide therapeutic index)
druggable proteins (new molecular "staples" can change the shape of
undruggable proteins to druggable)
changes in the cancer genome (cancerous genotypes and phenotypes
change over time)
Lecture 10: Personalized Medicine and
Biomarkers Personalized Medicine
common drugs have high non responder percentage for many diseases
shift from empiric medicine to individualized medicine
genetic polymorphisms affect pharmacokinetics and
pharmacodynamics Pharmacokinetic Variability
body converts codeine (prodrug) to morphine (active)
different individuals vary in how much codeine their body converts to morphine
“When a physician prescribes a known amount of codeine, what they’re really
prescribing
is an unknown amount of morphine, and that depends on the patient’s genetic
makeup.” Personalized Medicine
genetic tests are required for many personalized medicines
personalized medicine reshapes how we define "diseases"
biomarkers: indirect markers of internal state
o should be reliable: present in those with the condition and absent in those
without
o easily accessible (in a fluid such as urine)
o simple to detect with a standardized test
biomarkers are used for:
o risk assessment (am I at risk of this disease?)
o diagnosis (do I have the disease?)
o prognosis (what is the expected outlook of my
disease?) o predicting treatment response (will I
respond to this drug?) o pharmacokinetics (what
dosage should I take?)
o monitoring treatment response (how is my disease responding to the
treatment?) o recurrence (will this disease come back?)
example: urine test → pregnancy state
New York Times: Target Cancer Series
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Pcl102h1 spring 2013 the art of drug discovery. Hallmarks of cancer: growth signal autonomy (overgrowth) 2: evasion of apoptosis (avoiding cell suicide) Ignoring stop signals (ignoring tumor suppressor genes: angiogenesis (attracting blood vessels into tumor to deliver nutrients and carry away waste, unlimited replicative potential (telomere elongation, metastasis (invading other parts of the body) Cancer cells avoid detection by b cells and t cells adjuvant therapy: stimulating the immune system to make them hypersensitive. The action of the protein can be blocked by gleevec. Cml with certain mutations are gleevec resistant because gleevec can"t bind to them. Egfr (growth factor receptor) triggers cell growth and division when atp binds to it. Iressa binds to egfr by competitive inhibition. Cancer is a genetic disease because it is caused by dna mutations by chemicals, viruses/bacteria, or radiation. Malignant vs. benign tumors (only malignant can metastasize)
