ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Abiraterone treatment in castration-resistant prostate cancer selects for progesterone responsive mutant androgen receptors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01393730 (Phase II Trial of Abiraterone Acetate Combined With Dutasteride With Correlative Assessment of Tumor Androgen Levels and Androgen Receptor Sequence and Signaling at Baseline and at Progression), which is not on this map. Cited by 104 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase II Trial of Abiraterone Acetate Combined With Dutasteride With Correlative Assessment of Tumor Androgen Levels and Androgen Receptor Sequence and Signaling at Baseline and at Progression
Who cites it
104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 177 citations in OpenAlex.
- Androgen receptor mutations modulate activation by 11-oxygenated androgens and glucocorticoids.Prostate cancer and prostatic diseases · 2023Pooled it
- Loss of Wave1 gene defines a subtype of lethal prostate cancer.Oncotarget · 2015Pooled it
- Clinical Outcomes of First Subsequent Therapies After Abiraterone Acetate Plus Prednisone for High-Risk Metastatic Castration-Sensitive Prostate Cancer in the LATITUDE Study.Targeted oncology · 2023Trial
- Phase II Multicenter Study of Enzalutamide in Metastatic Castration-Resistant Prostate Cancer to Identify Mechanisms Driving Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Outcomes for Patients With SPOP Mutated Castration-Resistant Prostate Cancer (CRPC) Treated With an Androgen Receptor Pathway Inhibitor (ARPI).Clinical genitourinary cancer · 2026Article
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- Molecular mechanisms and classification of castration-resistant prostate cancer: Insights into androgen receptor, cancer stem cells, and neuroendocrine features.Current urology · 2026Article
- Spatially resolved transcriptomics identifies epithelial-specific oncogenic signaling networks in ameloblastoma.Journal of dental sciences · 2026Article
- Evolving roles for the androgen receptor and its protein interactome in castration-resistant prostate cancer.Oncogene · 2025Review
- Real-world effectiveness of darolutamide in metastatic castration-resistant prostate cancer.Endocrine-related cancer · 2025Article
- Nanoparticles with curcumin and piperine modulate steroid biosynthesis in prostate cancer.Scientific reports · 2025Article
- Increased nuclear factor I-mediated chromatin access drives transition to androgen receptor splice variant dependence in prostate cancer.Cell reports · 2025Article
- Newly developed preclinical models reveal broad-spectrum CDK inhibitors as potent drugs for CRPC exhibiting primary resistance to enzalutamide.Cancer science · 2024Article
- Targeting sex steroid biosynthesis for breast and prostate cancer therapy.Nature reviews. Cancer · 2023Review
- Targeting the Androgen Signaling Axis in Prostate Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Review
- A role for androgen receptor variant 7 in sensitivity to therapy: Involvement of IGFBP-2 and FOXA1.Translational oncology · 2023Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThe CYP17A1 inhibitor abiraterone markedly reduces androgen precursors and is thereby effective in castration-resistant prostate cancer (CRPC). However, abiraterone increases progesterone, which can activate certain mutant androgen receptors (AR) identified previously in flutamide-resistant tumors. Therefore, we sought to determine if CYP17A1 inhibitor treatment selects for progesterone-activated mutant ARs. EXPERIMENTAL
designAR was examined by targeted sequencing in metastatic tumor biopsies from 18 patients with CRPC who were progressing on a CYP17A1 inhibitor (17 on abiraterone, 1 on ketoconazole), alone or in combination with dutasteride, and by whole-exome sequencing in residual tumor in one patient treated with neoadjuvant leuprolide plus abiraterone.
resultsThe progesterone-activated T878A-mutant AR was present at high allele frequency in 3 of the 18 CRPC cases. It was also present in one focus of resistant tumor in the neoadjuvant-treated patient, but not in a second clonally related resistant focus that instead had lost one copy of PTEN and both copies of CHD1. The T878A mutation appeared to be less common in the subset of patients with CRPC treated with abiraterone plus dutasteride, and transfection studies showed that dutasteride was a more potent direct antagonist of the T878A versus the wild-type AR.
conclusionsThese findings indicate that selection for tumor cells expressing progesterone-activated mutant ARs is a mechanism of resistance to CYP17A1 inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.