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 () and Antonina Mitrofanova ()
Additional contact information
Sukanya Panja: Rutgers School of Health Professions
Mihai Ioan Truica: Northwestern University Feinberg School of Medicine
Christina Y. Yu: Rutgers School of Health Professions
Vamshi Saggurthi: Rutgers School of Health Professions
Michael W. Craige: Rutgers School of Health Professions
Katie Whitehead: Rutgers School of Health Professions
Mayra V. Tuiche: Rutgers School of Health Professions
Aymen Al-Saadi: Rutgers School of Engineering
Riddhi Vyas: Rutgers School of Health Professions
Shridar Ganesan: Rutgers Cancer Institute of New Jersey
Suril Gohel: Rutgers School of Health Professions
Frederick Coffman: Rutgers School of Health Professions
James S. Parrott: Rutgers School of Health Professions
Songhua Quan: Northwestern University Feinberg School of Medicine
Shantenu Jha: Rutgers School of Engineering
Isaac Kim: Rutgers Cancer Institute of New Jersey
Edward Schaeffer: Northwestern University Feinberg School of Medicine
Vishal Kothari: Northwestern University Feinberg School of Medicine
Sarki A. Abdulkadir: Northwestern University Feinberg School of Medicine
Antonina Mitrofanova: Rutgers School of Health Professions

Nature Communications, 2024, vol. 15, issue 1, 1-24

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-44686-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44686-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-44686-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().