Fig. 8: Model of therapy-induced senescence.

A Left: Canonical model of a switch-like transition between quiescence and senescence. We did not include an arrow from quiescence to senescence because it has not been clear in the field whether senescent cells can arise from existing quiescent cells or only from proliferating cells. Middle: Simple continuum model of cell-cycle withdrawal where quiescence and senescence represent different levels on the same continuum of withdrawal. Right: Model of cell-cycle arrest supported by this work. In the G0/G1 path, cells complete mitosis and first enter a shallow quiescence (G0). In this path, quiescent cells represent a reversible intermediate between proliferation and senescence and show a graded expression of senescence genes. In an alternative path, cells skip mitosis and arrest with 4 N DNA content. These cells transit directly to a senescent state, bypassing the quiescence deepening observed along the G0/G1 path.