AR Signaling and Cell Cycle Regulation in Prostate Cancer
Overview
The androgen signaling pathway is a key driver of PCa pathogenesis and progression1
Patients with mCRPC progress due to continued activation of the androgen receptor despite castrate levels of circulating testosterone2
Average life expectancy
2-3 YEARS3
Patients with mCRPC experience disease progression and cancer-specific mortality despite recent improvements4,5
Further research is needed to2:
Improve disease control
Delay the need for chemotherapy
Examples of current and emerging approaches in advanced PCa management
Targeting PMSA expression6
Co-targeting AR signalling and DNA repair through PARP inhibition7
Co-targeting AR and associated downstream elements7
Abbreviations
AR = androgen receptor; mCRPC= metastatic castrate resistant prostate cancer; PARP=poly (ADP-ribose) polymerase; PCa=prostate cancer; PI3K=phosphoinositide 3-kinase; PSMA=prostate-specific membrane antigen.
Related resources
Enhancing AR-Targeted Approaches
This animation provides an overview of the androgen receptor (AR) signaling pathway and its interaction with cell cycle regulation.
Enhancing AR-Targeted Approaches
This slide deck examines the unmet need in advanced prostate cancer, the AR pathway, its interaction with cell cycle regulation, and novel approaches to enhance AR-targeting.
Augmenting AR Inhibition in Prostate Cancer: Rationale for Targeting the Cell Cycle
This infographic provides an overview of the androgen receptor (AR) signaling pathway and the rationale to target the cell cycle in advanced prostate cancer.
References
- Lonergan PE, Tindall DJ. Androgen receptor signaling in prostate cancer development and progression. J Carcinog. 2011;10:20.
- Jernberg E, Bergh A, Wikström P. Clinical relevance of androgen receptor alterations in prostate cancer. Endocr Connect. 2017;6(8):R146-R161.
- Moreira DM, Howard LE, Sourbeer KN, et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017;15(1):60-66.e2.
- Nuhn P, De Bono JS, Fizazi K, et al. Update on Systemic Prostate Cancer Therapies: Management of Metastatic Castration-resistant Prostate Cancer in the Era of Precision Oncology. Eur Urol. 2019;75(1):88-99.
- https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.TPS198. Accessed June 2023.
- Wang F, Li Z, Feng X, Yang D, Lin M. Advances in PSMA-targeted therapy for prostate cancer [published correction appears in Prostate Cancer Prostatic Dis. 2021 Jul 6;:]. Prostate Cancer Prostatic Dis. 2022;25(1):11-26.
- Pisano C, Tucci M, Di Stefano RF, et al. Interactions between androgen receptor signaling and other molecular pathways in prostate cancer progression: Current and future clinical implications. Crit Rev Oncol Hematol. 2021;157:103
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