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Partial mechanisms of PARP inhibitor resistance in cancer. (A) PARG deletion leads to PARPI resistance. (B) Loss of SLFN11 enhances DSB repair capacity, ultimately leading to PARPi resistance. (C) The ATR/CHK/WEE1 signaling pathway arrests the cell cycle to reduce replication stress and promote DSB repair. (D) HR-deficient cells rely on MMEJ for DSB repair, which is mediated by POLθ. Inhibition of POLθ in HR-deficient cells results in cell death.
