SPOP mutations target STING1 signaling in prostate cancer and create therapeutic vulnerabilities to PARP inhibitor-induced growth suppression.
Chuandong GengMan-Chao ZhangGaniraju C ManyamJody V VykoukalJohannes F FahrmannShan PengCheng WuSanghee ParkShakuntala KondragantiDaoqi WangBrian D RobinsonMassimo LodaChristopher E BarbieriTimothy Anthony YapPaul Gettys CornSamir M HanashBradley M BroomPatrick G PiliéTimothy C ThompsonPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2023)
We provide evidence that SPOP is critical in regulating immunosuppressive versus anti-tumor activity downstream of DNA damage-induced STING activation in prostate cancer. PARPi treatment of SPOPmut CRPC alters this NC-STING signaling toward canonical, anti-tumor cGAS-STING-IFN-β signaling, highlighting a novel biomarker-informed treatment strategy for prostate cancer.