ラトガース・ヘルスで前立腺癌の治療効果を高める戦略を考案(Strategy to Boost Prostate Cancer Treatment Efficacy Devised at Rutgers Health)

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2024-01-22 ラトガース大学

ルトガース大学の研究者は、前立腺がん治療薬エンザルタミドの効果を予測し、治療の持続期間を延ばす戦略を開発した。エンザルタミドに効果がない患者と効果が一時的な患者の違いを解明し、エンザルタミドに抵抗する細胞ではMYCとNME2が関連していることを発見した。この研究は前立腺がん治療の進展であり、エンザルタミドに反応しない患者は他の薬剤に反応し、MYCの標的治療が治療効果を回復し、患者に利益をもたらすことが期待される。

<関連情報>

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

ラトガース・ヘルスで前立腺癌の治療効果を高める戦略を考案(Strategy to Boost Prostate Cancer Treatment Efficacy Devised at Rutgers Health)

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.

有機化学・薬学
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