Figure 4. Two alternative models of clonal TIC dynamics underlying long‐term growth of epithelial cancers in serial transplantation.

The classical cancer stem cell model defines extensive self‐renewal of long‐term TICs (LT‐TICs) as driving force within a hierarchically organized TIC compartment. The model of long‐term tumor growth in PDAC fundamentally differs from the classical stem cell model in that a succession of TIC clones drives tumor progression in serial xenotransplantation. Individual TICs only transiently contribute to tumor formation and produce mainly non‐tumorigenic progeny with very little or no self‐renewal. During long‐term tumor progression, inactive TIC clones are recruited to tumor formation and outcompete progeny of formerly active TIC clones.