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**XL309 + olaparib** is an investigational combination therapy being evaluated for the treatment of advanced solid tumors. XL309 is a potent, selective, orally bioavailable inhibitor of USP1, a deubiquitinating enzyme involved in DNA damage repair. Inhibiting USP1 impairs tumor cells' ability to repair DNA and may enhance cell death. Olaparib is a well-established oral small molecule inhibitor of PARP enzymes, which also play a key role in DNA repair. The combination aims to maximize anti-tumor efficacy by dual inhibition of DNA repair pathways, potentially increasing sensitivity to treatment in cancers with defective homologous recombination or DNA damage response. This combination is currently undergoing Phase 1 clinical investigation and is not FDA approved.
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