2024-01-22 ラトガース大学
<関連情報>
- https://www.rutgers.edu/news/strategy-boost-prostate-cancer-treatment-efficacy-devised-rutgers-health
- https://www.nature.com/articles/s41467-024-44686-5
メカニズム中心の制御ネットワークにより、CRPCにおけるエンザルタミド耐性のマーカーとしてNME2とMYCプログラムが特定される Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC
Sukanya Panja,Mihai Ioan Truica,Christina Y. Yu,Vamshi Saggurthi,Michael W. Craige,Katie Whitehead,Mayra V. Tuiche,Aymen Al-Saadi,Riddhi Vyas,Shridar Ganesan,Suril Gohel,Frederick Coffman,James S. Parrott,Songhua Quan,Shantenu Jha,Isaac Kim,Edward Schaeffer,Vishal Kothari,Sarki A. Abdulkadir & Antonina Mitrofanova
Nature Communications Published:08 January 2024
DO:Ihttps://doi.org/10.1038/s41467-024-44686-5
Abstract
Heterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is a central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise to elucidate markers of heterogeneous treatment response and salvage therapies for CRPC patients. Focusing on the de novo role of MYC as a marker of Enzalutamide resistance, here we reconstruct a CRPC-specific mechanism-centric regulatory network, connecting molecular pathways with their upstream transcriptional regulatory programs. Mining this network with signatures of Enzalutamide response identifies NME2 as an upstream regulatory partner of MYC in CRPC and demonstrates that NME2-MYC increased activities can predict patients at risk of resistance to Enzalutamide, independent of co-variates. Furthermore, our experimental investigations demonstrate that targeting MYC and its partner NME2 is beneficial in Enzalutamide-resistant conditions and could provide an effective strategy for patients at risk of Enzalutamide resistance and/or for patients who failed Enzalutamide treatment.
