ATR Inhibition Induces CDK1–SPOP Signaling and Enhances Anti–PD-L1 Cytotoxicity in Prostate Cancer

• Published in: Clinical cancer research Vol. 27; no. 17; pp. 4898 - 4909
• Main Authors: Tang, Zhe, Pilié, Patrick G., Geng, Chuandong, Manyam, Ganiraju C., Yang, Guang, Park, Sanghee, Wang, Daoqi, Peng, Shan, Wu, Cheng, Peng, Guang, Yap, Timothy A., Corn, Paul G., Broom, Bradley M., Thompson, Timothy C.
• Format: Journal Article
• Language: English
• Published: United States 01.09.2021
• Subjects: Animals; Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors; CDC2 Protein Kinase - physiology; Immune Checkpoint Inhibitors - therapeutic use; Male; Mice; Phthalazines - therapeutic use; Piperazines - therapeutic use; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; Prostatic Neoplasms - drug therapy; Repressor Proteins - physiology; Signal Transduction; Ubiquitin-Protein Ligase Complexes - physiology

Despite significant benefit for other cancer subtypes, immune checkpoint blockade (ICB) therapy has not yet been shown to significantly improve outcomes for men with castration-resistant prostate cancer (CRPC). Prior data have shown that DNA damage response (DDR) deficiency, via genetic alteration a...