Tumors develop in two distinct stages: (1) Initiation to Last-Common-Ancestor(LCA) where 6-8 “driver-mutations” occur sequentially over 10-50 years and (2) LCA to Metastasis where mutations occur more rapidly in parallel. In the first phase, mutations occur slowly and pierce 6-8 barriers to unrestrained growth by “hot-wiring” pro-growth pathways and then “shorting-out” pro-death pathways . In the second phase, genomic instability creates a large-heterogeneous-population that is well-equipped to compete against bigger-picture-limitations such as oxygen-availability, tissue-size, attacking immune cells and chemotherapies.
