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Updated: Apr 30, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Orteronel for the treatment of prostate cancer
Kathryn Van Hook1, Ted Huang, Joshi J Alumkal
1Division of Hematology & Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Abstract:
Orteronel (also known as TAK-700) is a novel hormonal therapy that is currently in testing for the treatment of prostate cancer. Orteronel inhibits the 17,20 lyase activity of the enzyme CYP17A1, which is important for androgen synthesis in the testes, adrenal glands and prostate cancer cells. Preclinical studies demonstrate that orteronel treatment suppresses androgen levels and causes shrinkage of androgen-dependent organs, such as the prostate gland. Early reports of clinical studies demonstrate that orteronel treatment leads to reduced prostate-specific antigen levels, a marker of prostate cancer tumor burden, and more complete suppression of androgen synthesis than conventional androgen deprivation therapies that act in the testes alone. Treatment with single-agent orteronel has been well tolerated with fatigue as the most common adverse event, while febrile neutropenia was the dose-limiting toxicity in a combination study of orteronel with docetaxel. Recently, the ELM-PC5 Phase III clinical trial in patients with advanced-stage prostate cancer who had received prior docetaxel was unblinded as the overall survival primary end point was not achieved. However, additional Phase III orteronel trials are ongoing in men with earlier stages of prostate cancer.
Insights
Orteronel, a novel hormonal therapy, targets androgen synthesis for prostate cancer treatment. While showing promise in early trials, a recent Phase III study did not meet its primary endpoint for overall survival.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Prostate cancer growth is often driven by androgens.
- Current androgen deprivation therapies have limitations.
- Novel agents targeting androgen synthesis are needed.
Purpose of the Study:
- To evaluate the efficacy and safety of orteronel (TAK-700) in prostate cancer treatment.
- To investigate orteronel's mechanism of inhibiting CYP17A1 and androgen synthesis.
- To assess orteronel's impact on prostate-specific antigen (PSA) levels and androgen suppression.
Main Methods:
- Orteronel inhibits the 17,20 lyase activity of CYP17A1.
- Preclinical studies assessed androgen suppression and organ shrinkage.
- Clinical trials evaluated orteronel's effect on PSA, androgen levels, and patient outcomes.
Main Results:
- Orteronel suppressed androgen levels and reduced prostate size in preclinical models.
- Clinical studies showed reduced PSA levels and more complete androgen suppression compared to conventional therapies.
- Fatigue was the most common side effect; febrile neutropenia was dose-limiting in combination therapy.
Conclusions:
- Orteronel demonstrates potent inhibition of androgen synthesis and has been generally well-tolerated as a single agent.
- The ELM-PC5 Phase III trial did not meet its overall survival endpoint in advanced prostate cancer patients.
- Further Phase III trials are ongoing to evaluate orteronel in earlier stages of prostate cancer.
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