AR splice variants in circulating tumor cells of patients with castration‐resistant prostate cancer: relation with outcome to cabazitaxel

Autor: Bram De Laere, Wendy Onstenk, Ron H.J. Mathijssen, Wytske M. van Weerden, Anieta M. Sieuwerts, Geert-Jan Creemers, John W.M. Martens, Ronald de Wit, Stefan Sleijfer, Paul Hamberg, Aart Beeker, Hielke J. Meulenbeld, Jaco Kraan, Guido Jenster, Luc Dirix, Mai Van, Corine M. Beaufort, Annemieke J.M. Nieuweboer
Přispěvatelé: Medical Oncology, Urology
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_treatment
Cell Count
Prostate cancer
0302 clinical medicine
Circulating tumor cell
androgen receptor
Medicine
Research Articles
AR splice variants
General Medicine
Neoplastic Cells
Circulating
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prostatic Neoplasms
Castration-Resistant
Treatment Outcome
Real-time polymerase chain reaction
Receptors
Androgen
Cabazitaxel
030220 oncology & carcinogenesis
Molecular Medicine
Taxoids
Research Article
medicine.drug
castration‐resistant prostate cancer
medicine.medical_specialty
circulating tumor cells
lcsh:RC254-282
03 medical and health sciences
SDG 3 - Good Health and Well-being
Internal medicine
Genetics
Humans
Aged
Chemotherapy
Taxane
business.industry
cabazitaxel
Prostate-Specific Antigen
medicine.disease
Survival Analysis
Reverse transcriptase
Androgen receptor
Alternative Splicing
030104 developmental biology
Human medicine
business
Zdroj: Molecular Oncology, Vol 13, Iss 8, Pp 1795-1807 (2019)
Molecular Oncology
Molecular Oncology, 13(8), 1795-1807. John Wiley & Sons Ltd.
ISSN: 1574-7891
1878-0261
Popis: The androgen receptor splice variant (AR-V) 7 in circulating tumor cells (CTCs) is a predictor for resistance to anti-AR-targeted treatment, but not to taxane-based chemotherapy in metastatic castration-resistant prostate cancer (mCRPC). In this study, we investigated whether the presence of two constitutively active variants (AR-V3, AR-V7) and two other conditionally activated variants (AR-V1, AR-V9) vs full-length androgen receptor (AR-FL) measured in CTCs from patients with mCRPC were associated with outcome to therapy with the taxane cabazitaxel. Blood was collected at baseline and after two cycles of cabazitaxel from 118 mCRPC patients starting cabazitaxel in a prospective phase II trial. CellSearch-enriched CTCs were enumerated and in parallel characterized for the presence of the AR-Vs by reverse transcription quantitative polymerase chain reaction. Correlations with CTC and prostate-specific antigen response to cabazitaxel as well as associations with overall survival (OS) were investigated. All AR-Vs were frequently present and co-expressed at frequencies of 31-48% at baseline and at 19-40% after two cycles of cabazitaxel. No specific directions of change in the measured variants were detected between the start of treatment and after two cycles of cabazitaxel. No associations between the presence of AR-V3 and AR-V7 and outcome to cabazitaxel were observed. While a reduction in CTCs to < 5 CTCs during treatment (CTC5-response) was less often observed in patients with AR-V9-positive CTCs at baseline (P = 0.004), the CTC5-adjusted detection of AR-V1 after two cycles of cabazitaxel was an independent prognostic factor for OS [HR 2.4 (95% CI 1.1-5.1, P = 0.03)]. These novel findings are expected to contribute to more personalized treatment approaches in mCRPC patients.
Databáze: OpenAIRE
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