Fig. 8: Proliferation signal modulation over a treatment cycle.
Proliferation signal, p, during the third treatment cycle with yellow highlight for locations where p ≥ hp (proliferation window) and black highlight for locations where p < hd (death window). Representative eradication (E), survival (S) and persistence (P) niches are the same as in Figs. 5 and 7. a At the start of the drug delivery period all three niches contain locations where the proliferation signal is above hd, forming a bulk region in the survival and persistence niches, and small sparse clusters in the eradication niche. Regions in the proliferative window are only present in the survival niche. b In the middle of the drug delivery period a small number of locations in the survival niche remain in the proliferative window. The proliferation signal in the eradication and persistence niches is significantly depleted, with no locations in the proliferative window. c By the end of the drug delivery period in the survival niche the region in the proliferative window has increased through cancer proliferation and further stroma activation. The eradication niche is almost entirely in the death window, although limited regions in the proliferation window indicate late activation of stroma. There are no such locations in the persistence niche, which is largely in the quiescent window. d Towards the end of the drug holiday period, in the eradication and persistence niches no locations are in the proliferative window. In the survival niche the region in the proliferative window which appeared during drug delivery expands further, while other locations move from the death to the quiescent window.
