1. Cancer

2. Cell Cycle G0 is resting phase Platelets are necessary for blood clotting Platelets also release growth factors to start cell growth at the sides of the wound One of the most important factor is Platelet derived growth factor PDGF PDGF is an important growth factor for fibroblasts (cells that make connective tissue) Once cells pass restriction point, they will go all the way around the growth cycle until they look for growth factor again

3. Mitosis Restriction point at the end of G1 G1 G0 Growth Inhibitors M M In the absence of growth factors S S In the presence of growth factors G2 Restriction Point

4. PDGF Receptors PDB 1h9o >1H9O:B|PDBID|CHAIN|SEQUENCE YVPML >1H9O:A|PDBID|CHAIN|SEQUENCE GSPIPHHDEKTWNVGSSNRNKAENLLRG KRDGTFLVRESSKQGCYACSVVVDGEVKH CVINKTATGYGFAEPYNLYSSLKELVLHYQH TSLVQHNDSLNVTLAYPVYAQQRR

5. Cancer Cells Deregulated growth Release Growth Factors for their own Growth factor receptors Larger number of growth factor receptors – Overexpressed normal 500, in carcinomas 100,000 Truncated receptors – Fire constitutively (not regulated)

6. Cancer Drugs Iressa - only 10% responded (those who had mutation that caused structural alterations) Iressa® was reported to be effective in 24 or 29 patients with EGFR mutations compared to 2 of 21 patients without these mutations. Those who did respond had truncated external receptors

7. Cancer Human cells 3*10 13 Tumor cells 10 9 – All cells in tumor mass descend from one mutated cell – They form populations from genetic material of a single ancestor Normal Cells have contact inhibition – The signal growth stoppage when receptors detect another cell in contact Cancerous cells do not have planar growth

8. Cell Transformation Random Mutations Mutagens – Smoking, xrays, drugs increase mutation probability When a mutation hits in one of these sites, you can get uncontrolled growth