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LP-184 + olaparib is an investigational combination therapy comprised of LP-184, a synthetically lethal small molecule, and olaparib, an FDA-approved poly(ADP-ribose) polymerase (PARP) inhibitor. LP-184 exerts its therapeutic effect by inducing DNA double-strand breaks via PTGR1-mediated activation, particularly benefiting cancers with DNA damage repair (DDR) gene alterations, including those resistant to PARP inhibitors. Olaparib inhibits PARP1 and PARP2, essential for DNA repair, leading to synthetic lethality in BRCA1/2-mutated tumors. The combination is being clinically evaluated for enhanced activity, especially in advanced triple-negative breast cancer (TNBC) with BRCA1/2 alterations, aiming to overcome PARP inhibitor resistance and improve outcomes in molecularly defined subgroups[1][3][5][7].
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