Figure 2: Radio- or chemotherapy induces cancer cell apoptosis generating proliferation signals that drive the rapid proliferation of surviving cancer cells which repopulate the tumour by generating signals that act directly on stem/progenitor cells or by recruiting macrophages (a). The role of PUMA in compensatory proliferation has led to the suggestion that blocking caspase-mediated cleavage of iPLA2 with small molecule caspase inhibitors may improve patient outcomes by preventing this compensatory proliferation. However the general applicability of this model is uncertain for several reasons. Firstly, in Drosophila development blocking apoptosis in some circumstances produces undead cells whose persistent signalling increases compensatory proliferation (b). Secondly, while caspase inhibitors block apoptosis, the irradiated or drug-treated cells may still die by nonapoptotic processes or become senescent, which may induce compensatory proliferation as well (c).