A two-year note on reprogramming cancer cells

We have been running a pair of Yamanaka factors on cancer cells for about two years now. The design is almost naive: take a cell that has de-differentiated into a tumour lineage, and give it enough of a push toward a more committed state that it cannot sustain its own transcriptional contradictions. Many of them die. Not all. The ones that survive are telling.

This is the main internal aging programme, but we are validating it in glioblastoma first. GBM is unforgiving — a good test of whether the mechanism translates. We are not trying to reprogram GBM to anything useful; we are trying to give the cell an order to be a thing, and then watching which orders it can tolerate.

Reprogramming as aging therapy is a reasonable conjecture. But reprogramming as a selective pressure, in the Yamanaka-factor sense — that, I think, is the more important idea, and the one we are still working out. Cancer cells are good at ignoring instructions. The ones that cannot ignore a fate-command are the ones we want to kill.