1. VogelsteinScience15Apr13.ppt Updated: April 15, 2013 Why Is Cancer Therapy Such a Difficult and Often Intractable Effort? Cancer Genome Landscapes. Science, Vol. 339, March 29, 2013, pp 1546 – 1548 Bert Vogelstein, Nickolas Papadopoulos, Victor Velculescu, Shibin Zhou, Luis Diaz, Kenneth W. Kinzler Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore

2. Number of somatic mutations associated with cancers in patients

3. From 5 or 10 to 130 to 700 mutations per tumor

4. (Insertions & deletions) ( Single base substitutions )

6. Signaling Pathways Affected In Cancers

7. Pathway Anomalies in Progression in Colo-Rectal Cancer

8. The RAS Pathway as a representative signaling pathway affected by cancer mutations and approaches to therapy based on RAS pathway anomalies RTK = receptor tyrosine kinase