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    Association details:
    Biomarker:TP53 mutation
    Cancer:Solid Tumor
    Drug:peposertib (M3814) (DNA PK inhibitor) +
    novobiocin (VP-006) (DNA polymerase theta inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    Cancer Res
    Title:

    Targeting DNA Repair with Combined Inhibition of NHEJ and MMEJ Induces Synthetic Lethality in TP53-Mutant Cancers

    Published date:
    10/17/2022
    Excerpt:
    Consequently, the combination of peposertib plus novobiocin resulted in synthetic lethality in TP53-deficient tumor cell lines, organoid cultures, and patient-derived xenograft models. Thus, the combination of a targeted DNA-PK/NHEJ inhibitor with a targeted POLθ/MMEJ inhibitor may provide a rational treatment strategy for TP53-mutant solid tumors.
    DOI:
    10.1158/0008-5472.CAN-22-1124