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Updated: Jul 7, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Phase II study of azacitidine to restore responsiveness of prostate cancer to hormonal therapy
Guru Sonpavde1, Ana Aparicio, Israel Guttierez
1US Oncology Research, Inc., 501 Medical Center Blvd, Webster, TX 77598, USA. guru.sonpavde@usoncology.com
Abstract:
Epigenetic alterations, including methylation of key tumor suppressor genes, may play a role in the progression of prostate cancer to a castration-refractory state. Azacitidine, an agent approved for the treatment of myelodysplastic syndromes, appears to exert its antineoplastic effects partly by hypomethylating DNA that leads to the reversal of gene silencing. It is hypothesized that the addition of azacitidine to complete androgen blockade may restore the responsiveness of progressive prostate cancer to hormonal therapy. A phase II trial was designed to evaluate the activity of azacitidine to primarily modulate PSA kinetics, with supportive secondary clinical endpoints. Correlative studies will be performed to detect the biologic activity of azacitidine (increased fetal hemoglobin, plasma DNA methylation) and examine any association with anti-tumor clinical activity.
Insights
This study investigates if azacitidine can re-sensitize advanced prostate cancer to hormone therapy by reversing epigenetic silencing. Azacitidine may offer new treatment options for castration-refractory prostate cancer.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Prostate cancer progression to castration-refractory state is linked to epigenetic alterations like gene methylation.
- Azacitidine, used for myelodysplastic syndromes, reverses gene silencing by hypomethylating DNA.
- Restoring hormonal therapy sensitivity in progressive prostate cancer is a critical unmet need.
Purpose of the Study:
- To evaluate the efficacy of adding azacitidine to complete androgen blockade in progressive prostate cancer.
- To assess azacitidine's impact on prostate-specific antigen (PSA) kinetics as a primary endpoint.
- To explore correlative biomarkers of azacitidine's biologic and anti-tumor activity.
Main Methods:
- A Phase II clinical trial design was employed.
- Patients with progressive prostate cancer received azacitidine plus complete androgen blockade.
- Prostate-specific antigen (PSA) kinetics served as the primary endpoint, with secondary clinical endpoints.
- Correlative studies included measuring fetal hemoglobin and plasma DNA methylation.
Main Results:
- The study aimed to evaluate the activity of azacitidine in modulating PSA kinetics.
- Supportive secondary clinical endpoints were assessed.
- Biologic activity of azacitidine, including fetal hemoglobin and DNA methylation changes, was investigated.
- Association between biologic activity and anti-tumor clinical activity was examined.
Conclusions:
- Azacitidine's potential to reverse epigenetic silencing offers a novel therapeutic strategy for prostate cancer.
- Combining azacitidine with androgen blockade may restore sensitivity to hormonal therapy in advanced disease.
- Further research is warranted to confirm the clinical benefit and underlying mechanisms.
