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Ovarian cancer cells with RAS/PI3K pathway mutations have chronically low NAD⁺ levels, making them highly vulnerable to a dual‑therapy strategy that combines PARP inhibition (olaparib) with NAMPT inhibition (FK866)

This new research published in is a collaboration between Chemistry, Surgery and Cancer, and Metabolism Departments at ������ý. The paper shows that by blocking both DNA repair and NAD⁺ salvage with PARP/NAMPT inhibitors, the combination drives catastrophic NAD⁺ depletion, oxidative stress, DNA damage, and apoptosis, producing far stronger anti‑tumour effects than either drug alone. In mouse models, this synergy significantly reduced tumour burden and extended survival without major toxicity, suggesting that RAS/PI3K mutations could serve as biomarkers to safely deploy NAMPT inhibitors at lower doses and broaden the clinical impact of PARP‑based therapies.

Congratulations Michael Gruet on this first author publication! This research was supported by funding from EPSRC, Cancer Research UK Convergence Science Centre and Ovarian Cancer Action.