AR Signaling and Cell Cycle Regulation in Prostate Cancer
AR Signaling and the Cell Cycle
The interaction between AR and other molecular pathways results in PCa cell cycle progression and cancer proliferation1,2
Signaling through the AR pathway in PCa includes overexpression of Cyclin D1 and subsequent activation of CDK4/63,4
Upregulation of Cyclin D1 is a potential mechanism of resistance to novel AR-targeting agents5
Transition from G1 to S phase is a key checkpoint for regulation of the cell cycle6
Beyond the restriction (R) point, cells become “committed” to the cell cycle and progress autonomously6,7
AR=androgen receptor; CDK4/6=cyclin dependent kinase 4 & 6; D=dihydrotestosterone; E2F=E2F family of transcription factors; P=phosphorylation; PCa=prostate cancer; PI3K=phosphoinositide 3-kinase; R=restriction point; Rb=retinoblastoma protein.
Enhancing AR-Targeted Approaches
This animation provides an overview of the androgen receptor (AR) signaling pathway and its interaction with cell cycle regulation.
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.
This infographic provides an overview of the androgen receptor (AR) signaling pathway and the rationale to target the cell cycle in advanced prostate cancer.
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- Kase AM, Copland Iii JA, Tan W. Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer. Onco Targets Ther. 2020;13:10499-10513.
- Balk SP, Knudsen KE. AR, the cell cycle, and prostate cancer. Nucl Recept Signal. 2008;6:e001.
- Wander SA, O’Brien N, Litchfield L, et al. Targeting CDK4 and 6 in cancer therapy: Emerging preclinical insights related to abemaciclib. Oncologist. 2022;27:811-821.
- Pal SK, Patel J, He M, et al. Identification of mechanisms of resistance to treatment with abiraterone acetate or enzalutamide in patients with castration-resistant prostate cancer (CRPC). Cancer. 2018;124(6):1216-1224.
- Duronio RJ, Xiong Y. Signaling pathways that control cell proliferation. Cold Spring Harb Perspect Biol. 2013;5(3):a008904.
- Mullany LK, White P, Hanse EA, et al. Distinct proliferative and transcriptional effects of the D-type cyclins in vivo. Cell Cycle. 2008;7(14):2215-2224.