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Updated: May 30, 2026
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Published on: February 27, 2015
Androgen quantitation in prostate cancer tissue using liquid chromatography tandem mass spectrometry
1Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA. Mark.Titus@RoswellPark.org
Abstract:
Prostate cancer that recurs after androgen deprivation therapy is the second leading cause of cancer-related death in North American men. Clinical and experimental evidences indicate that the development of recurrent prostate cancer is dependent on re-activation of the androgen receptor signaling pathway. Androgen is required for androgen receptor translocation to the nucleus, interaction with androgen response elements, expression of target genes, and prostate cancer cell proliferation. The intra-tissue and serum testosterone and dihydrotestosterone levels are important biomarkers to monitor androgen deprivation therapy efficacy in prostate cancer and recurrent prostate cancer. We have measured testosterone and dihydrotestosterone in procured recurrent prostate cancer specimens using liquid chromatography tandem mass spectrometry. The measured androgen levels are sufficient to activate androgen receptor and suggest that the recurrent prostate cancer microenvironment is capable of intracrine androgen biosynthesis.
Insights
Recurrent prostate cancer after androgen deprivation therapy reactivates androgen receptor signaling. Intratumoral androgens are sufficient to activate this pathway, indicating local biosynthesis in the recurrent prostate cancer microenvironment.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Prostate cancer recurrence after androgen deprivation therapy (ADT) is a major cause of cancer death.
- Reactivation of androgen receptor (AR) signaling is critical for recurrent prostate cancer development.
- Androgens are essential for AR translocation, DNA binding, gene expression, and prostate cancer cell proliferation.
Purpose of the Study:
- To investigate the role of intracrine androgen biosynthesis in recurrent prostate cancer.
- To measure intra-tissue androgen levels in recurrent prostate cancer specimens.
- To determine if measured androgen levels are sufficient to activate the AR signaling pathway.
Main Methods:
- Procurement of recurrent prostate cancer specimens.
- Quantification of intra-tissue testosterone and dihydrotestosterone using liquid chromatography tandem mass spectrometry (LC-MS/MS).
Main Results:
- Intra-tissue levels of testosterone and dihydrotestosterone were measured in recurrent prostate cancer.
- The quantified androgen levels were found to be sufficient for AR activation.
- These findings suggest the capability of intracrine androgen biosynthesis within the recurrent prostate cancer microenvironment.
Conclusions:
- The recurrent prostate cancer microenvironment can locally synthesize androgens.
- Intracrine androgen biosynthesis contributes to AR reactivation in recurrent prostate cancer.
- Targeting intracrine androgen production may offer new therapeutic strategies for recurrent prostate cancer.
