I don’t think this is targeting a mutated version of PCNA… that would assume that all cancers had the same mutation.
Instead, this would target both healthy and cancerous cells. However, the idea is that the cancer cells are more susceptible to the drug. Healthy cells will be affected, but cancer cells will be affected more, and are more unstable, so losing PCNA will have more of an effect on the cancer cells.
The main idea is to do as much damage to the cancer cells while doing as little to normal cells as possible.
Edit: after reading the paper, the drug is targeting a cancer specific isoform of PCNA. This isn’t a mutation, but a slightly different form of the existing protein. Cancers tend to rely on this specific version, while healthy cells can use a different isoform (or both?). A selective inhibitor for this isoform would be cancer cell specific. There would still be some effect on healthy cells, but not as much as with a traditional cytotoxic chemotherapy.
I read it selectively initiates apoptosis based on that protein and only affects cancer cells but that might have been relayed incorrectly
Edit: exactly -> "It was created to target a specific variant of PCNA found only in cancer cells. This protein is crucial in the body for DNA repair, but targeting it was difficult because of its role in healthy cells. By going after only the variant, it may be possible to selectively target only cancer cells"
>"Moreover, the identification of a distinct isoform of PCNA associated with cancer cells has potentially opened a novel avenue for the development of new chemotherapeutics"
A distinct isoform does not necessarily mean a mutation.
The coding sequence for an isoform is part of the normal gene DNA sequence, but the cells can “choose” which version to make. In this case the caPCNA isoform is the form predominantly expressed in cancer cells.
(There is a mechanism where novel splicing isoforms can be produced by a mutation, but this doesn’t seem to be one of those.)
Instead, this would target both healthy and cancerous cells. However, the idea is that the cancer cells are more susceptible to the drug. Healthy cells will be affected, but cancer cells will be affected more, and are more unstable, so losing PCNA will have more of an effect on the cancer cells.
The main idea is to do as much damage to the cancer cells while doing as little to normal cells as possible.
Edit: after reading the paper, the drug is targeting a cancer specific isoform of PCNA. This isn’t a mutation, but a slightly different form of the existing protein. Cancers tend to rely on this specific version, while healthy cells can use a different isoform (or both?). A selective inhibitor for this isoform would be cancer cell specific. There would still be some effect on healthy cells, but not as much as with a traditional cytotoxic chemotherapy.