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SYN818 + olaparib is an investigational oral combination therapy currently being evaluated in a Phase Ib clinical trial for adult patients with locally advanced or metastatic solid tumors harboring mutations in BRCA or defects in the homologous recombination repair (HRR) pathway[1][3][5][7]. Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor, approved for the treatment of several cancers with DNA repair deficiencies, including BRCA-mutated ovarian, breast, pancreatic, and prostate cancers[2][6][8][10]. SYN818’s specific molecular profile and mechanism have not been disclosed; however, it is presumed to target a pathway synergistic with PARP inhibition in HRR-deficient tumors. The combination aims to enhance DNA repair inhibition and synthetic lethality in tumor cells with defective homologous recombination, leveraging olaparib’s mechanism as a selective inhibitor of PARP1 and PARP2, which induces DNA damage and cell death particularly in repair-deficient tumor cells[2][6][8][10].
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