Can treatment-tolerant cancer cells become temporarily more mutable?
In colorectal-cancer models, a small population of cells that persists during targeted treatment temporarily changed DNA-repair programmes. It is an intriguing mechanism, but its contribution to resistance in patients is still not settled.
Written retrospectively and published on August 3, 2026.
Background reading, not clinical guidance. This describes published research; it is not a recommendation for any individual case, and the cited studies may have been superseded.
Resistance is often described as selection of a resistant clone that was already present. That is a well-documented route, but laboratory studies suggest a second possibility: a small drug-tolerant population may temporarily enter a state in which it makes more genetic errors.
In 2019, researchers studying colorectal-cancer models exposed to EGFR-targeted treatment found that persister cells reduced expression of mismatch-repair and homologous-recombination genes while increasing error-prone DNA polymerases. The changes reversed after treatment was withdrawn.
A careful reading of the numbers
The 2019 study showed altered repair capacity and reporter evidence of increased mutability; it did not report a global fold increase in point mutations. A 2022 follow-up estimated a temporary 7- to 50-fold increase in mutation rate in two cell-line settings. That number should not be retroactively attributed to the earlier study.
Neither experiment proved that this state creates the specific resistance mutations seen in patients. It may operate alongside the expansion of pre-existing resistant cells, and its relative importance in real tumours remains unknown.
Comments
Threads are public and indexed — please keep personal medical data out of them. Found a clinical error? Open an issue instead.
Comments are not switched on yet — the backend still needs to be configured.