The final barrier.

When senescence and all other checkpoints fail, replicative crisis is the last ditch effort cells muster before full-blown malignant transformation. And this is truly no less than a crisis for rogue cells, as it is exceedingly rare to come out the other end with your reproductive integrity intact, meaning the nitty gritty details may offer an intriguing gateway to expanding our armamentarium against cancer—at least for the basic scientists among us. The rest of us will have to take their word for it. This report is all about elucidating the mechanisms of replicative crisis, and apparently the critical step is none other than autophagy. Bypassing this one step bypassed the crisis altogether. What’s more, the trigger for autophagy didn’t lie in the usual suspect of chromosomal damage but rather in telomere damage, which initiated a cytosolic cell-signaling cascade. TBL: Novel targets to ensure effective autophagy could halt and maybe even prevent cancer progression. | Nassour, Nature 2019