“…Finally, if our proposal that cellular stemness modulates reoviral oncolysis is correct, we are left with the challenge of reconciling this explanation with that of Lee’s group, which earlier posited a critical role for Ras pathway activation in promoting reoviral oncolysis [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. As we and others have observed (see our accompanying manuscript [ 94 ]), the correlation between Ras activation and reoviral activity is good but imperfect, with many exceptions. Thus we are led to speculate that cells able to adapt to chronic Ras-mediated signalling may become cancerous, in part, by sometimes activating stemness pathways that also confer reoviral susceptibility.…”