Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer
Abstract
:1. Introduction
1.1. Advanced/Recurrent Prostate Cancer Standard of Care: Advancements and Shortcomings
1.2. Friend and Foe: Rethinking the Complex Role of Androgen Signaling in Prostate Cancer
1.3. Contributions from the Laboratory That Support Testosterone Therapy in CRPC
1.4. Preclinical Studies Indicate That Prostate Cancer Carefully Titrates Androgen Signaling
1.5. Heterogeneity of AR Expression Accompanies the Failure of Manipulation of Androgen Status
1.6. Models of High Testosterone Resistance
2. Materials and Methods
2.1. Cell Lines
2.2. Selection of LNCaP Variants
2.3. Western Blots
2.4. Immunohistochemistry
2.5. Tumor Xenograft Studies
3. Discussion
4. Conclusions
Supplementary Materials
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cell Line | Parent | Selection | Phenotype |
---|---|---|---|
P0 | LNCaP | ARE-luc | wild type |
P1 | P0 | low androgen | CRPC |
P1R1/R | P1 | high androgen | HTR |
P1R1/R * | P1R1/R | low androgen | AI |
M0 | LNCaP | ARE-luc | wild type |
M1 | M0 | low androgen | CRPC |
M1R1/R | M1 | high androgen | HTR |
M1R1/R * | M1R1/R | low androgen | AI |
M2 | M0 | low androgen | CRPC |
M2R1/R | M2 | high androgen | HTR |
M2R1/R * | M2R1/R | low androgen | AI |
4D1 | LNCaP | enzalutamide | enz-resistant |
4D1enz1 | 4D1 | low androgen | CRPC |
4D1enz1/R | 4D1enz1 | high androgen | HTR |
4D1enz1/R * | 4D1enz1/R | low androgen | AI |
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Nordeen, S.K.; Su, L.-J.; Osborne, G.A.; Hayman, P.M.; Orlicky, D.J.; Wessells, V.M.; van Bokhoven, A.; Flaig, T.W. Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer. Life 2021, 11, 884. https://doi.org/10.3390/life11090884
Nordeen SK, Su L-J, Osborne GA, Hayman PM, Orlicky DJ, Wessells VM, van Bokhoven A, Flaig TW. Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer. Life. 2021; 11(9):884. https://doi.org/10.3390/life11090884
Chicago/Turabian StyleNordeen, Steven K., Lih-Jen Su, Gregory A. Osborne, Perry M. Hayman, David J. Orlicky, Veronica M. Wessells, Adrie van Bokhoven, and Thomas W. Flaig. 2021. "Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer" Life 11, no. 9: 884. https://doi.org/10.3390/life11090884
APA StyleNordeen, S. K., Su, L. -J., Osborne, G. A., Hayman, P. M., Orlicky, D. J., Wessells, V. M., van Bokhoven, A., & Flaig, T. W. (2021). Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer. Life, 11(9), 884. https://doi.org/10.3390/life11090884