Unpublished draft

One-Hit Cancer

The Historical Discovery

In 1953-1954, epidemiologists discovered that cancer incidence increases roughly as the sixth power of age—doubling someone’s age increases cancer risk 64-fold, not 2-fold. This suggested cancer requires approximately 6-7 sequential “hits,” each with constant probability over time.

Modern cancer genomics validated this multi-hit model while revising numbers downward: epithelial cancers typically need 3-5 driver mutations, blood cancers often just 1-2. But can we go lower?

The Architecture-Defense Tradeoff

Different tissues evolved different coordination architectures, creating natural variation in required “hits”:


5-Hit Cancer: Pancreatic Ductal Adenocarcinoma (PDAC)

The tissue type: Pancreatic duct epithelial cells that form organized tubes secreting digestive enzymes. These cells must