Turn off the error-prone repair that manufactures resistance mutations
Under treatment stress, cancer cells switch on sloppy DNA copying that generates the mutations they need to survive. Blocking that machinery could stop resistance being invented.
Stress-induced mutagenesis through translesion synthesis polymerases (REV1, POLZ) accelerates the emergence of resistance in bacteria and in cancer cells. REV1 inhibitors have been described and shown to reduce chemotherapy-induced mutagenesis and delay resistance in models. Given as an adjunct rather than a cytotoxic, the aim is to lower the mutation supply rate rather than to kill cells.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
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not linked directly; found by shared links- IdeaCut off the emergency programme cancer cells use to survive treatment
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy.
- IdeaBlock the chemical switch that lets cells hide from treatment
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy.
- IdeaSlow the tumour's mutation engine with APOBEC inhibitors during targeted therapy
Shares Mutational signature, Acquired resistance to every therapy.
- IdeaMake post-progression sampling a condition of accelerated approval
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy.
- IdeaKill the sleeping survivor cells with iron-dependent cell death
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy.
- IdeaEvery resistance mechanism found in a patient must be rebuilt in the laboratory
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy.
- IdeaSMART designs to test treatment strategies, not just single drugs
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy.
- IdeaStarve the survivors: target the energy pathway drug-tolerant cells switch to
Shares Drug resistance (primary and acquired), Acquired resistance to every therapy.