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Cancers with faulty DNA proof-reading depend on one particular unwinding enzyme to survive. Blocking it kills them and spares normal cells.
Microsatellite-unstable cancers accumulate expanded TA repeats that form secondary structures requiring WRN helicase to resolve; WRN loss is selectively lethal in MSI-high lines, one of the strongest synthetic-lethal signals from CRISPR screens. WRN inhibitors and degraders have entered early clinical trials. The strategic proposal is to test WRN inhibition specifically in MSI-high tumours that have failed immunotherapy, a group with no good options.
Shares Drugging the 'undruggable' cancer targets, Synthetic lethality, Synthetic lethality approaches, CRISPR functional genomics.
Shares Synthetic lethality, Synthetic lethality approaches, CRISPR functional genomics, The undruggable drivers.
Shares Synthetic lethality, Synthetic lethality approaches, CRISPR functional genomics, The undruggable drivers.
Shares Mismatch-repair-deficient endometrial cancer, Mismatch-repair deficient (MSI-high) colorectal cancer, Endometrial cancer, Colorectal cancer.
Shares Drugging the 'undruggable' cancer targets, CRISPR functional genomics, The undruggable drivers.
Shares Synthetic lethality, Synthetic lethality approaches, CRISPR functional genomics, Mismatch-repair deficient (MSI-high) colorectal cancer.
Shares Synthetic lethality, Synthetic lethality approaches, CRISPR functional genomics.
Shares Mismatch-repair-deficient endometrial cancer, Mismatch-repair deficient (MSI-high) colorectal cancer, Endometrial cancer, Colorectal cancer.