Summary PCL102H Exam Notes Section 1

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