Targeting DNA2 Overcomes Metabolic Reprogramming in Multiple Myeloma.
Natthakan ThongonFeiyang MaPamela LockyerNatalia BaranJintan LiuChristopher JacksonAshley RoseBethany WildemanMatteo MarchesiniValentina MarchicaPaola StortiNicola GiulianiIrene Ganan-GomezVera AdemaYun QingMin HaRodrigo FonsecaCaleb ClassLin TanRashmi Kanagal-ShamanaDavid Berrios NolascoClaudio CerchioneGuillermo Montalban-BravoAndrea SantoniCarlos Bueso-RamosMarina KonoplevaPhilip LorenziGuillermo Garcia-ManeroElisabeth ManasanchAndrea VialeMarta ChesiSimona CollaPublished in: bioRxiv : the preprint server for biology (2023)
Metabolic reprogramming is a mechanism through which cancer cells maintain survival and become resistant to DNA-damaging therapy. Here, we show that targeting DNA2 is synthetically lethal in myeloma cells that undergo metabolic adaptation and rely on oxidative phosphorylation to maintain survival after DNA damage activation.