Well 5-FU has been around for over 50 Years. Almost if not everyone on this forum has most likely experienced its use. Seems its not too old a drug to determine more about its function and maybe learn more about ways it might be able to be applied or enhanced through the use of these other recently discovered mechanisms of action. Here is a commentary from one of my favorite blogs about drug discovery. Finally after over a year the Blog owner is back to talking drug research instead of Covid!!! Here is a link. Its pretty technical.
https://blogs.sciencemag.org/pipeline/a ... -you-think
This article as usual links back to the original paper, but its behind a pay wall. Generally speaking the article indicates that unlike was primarily thought to be the mechanism via inhibition of thymidylate synthase. See: https://en.wikipedia.org/wiki/Thymidylate_synthase that actually many of its actions seem to be on RNA signaling, rather than just its messing with DNA repair.
So - There might still be life in this old drug yet, especially if they manage to fine more ways to tune its activity by using these findings. Perhaps they will be able to test precisely when this will become no longer effective. Maybe add another drug that makes it so again by inhibiting another pathway?
Good luck
GrouseMan