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0The research paper identifies a critical biological mechanism behind PARP inhibitor (PARPi) resistance in ovarian cancer, focusing on the USP14–SLC1A5 axis. The study reveals that SLC1A5, a protein responsible for glutamine transport, is frequently overexpressed in resistant cancer cells and contributes to their survival by fueling glutamine metabolism. This metabolic shift enhances DNA repair and reduces oxidative stress, allowing tumors to withstand treatment with drugs like olaparib. Scientists discovered that the enzyme USP14 directly stabilizes SLC1A5 by preventing its degradation, thereby maintaining high levels of the transporter. Experimental results show that inhibiting this pathway, specifically using the SLC1A5 inhibitor V-9302, can successfully resensitize ovarian cancer cells to therapy. Ultimately, the research suggests that combining metabolic targeting with standard inhibitors offers a powerful new strategy to improve outcomes for patients with advanced disease.
References:
Han F, Du H, Tian K, et al. Targeting SLC1A5-mediated glutamine metabolism overcomes PARP inhibitor resistance in ovarian cancer[J]. Cell Death & Disease, 2026.
