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
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
