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

Autor: Sieuwerts AM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.; Department of Medical Oncology, Cancer Genomics Netherlands, Rotterdam, The Netherlands., Onstenk W; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Kraan J; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Beaufort CM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Van M; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., De Laere B; GZA Hospitals Sint-Augustinus, Wilrijk, Belgium.; Center for Oncological Research, University of Antwerp, Antwerp, Belgium., Dirix LY; GZA Hospitals Sint-Augustinus, Wilrijk, Belgium.; Center for Oncological Research, University of Antwerp, Antwerp, Belgium., Hamberg P; Department of Internal Medicine, Franciscus Gasthuis and Vlietland, Rotterdam, The Netherlands., Beeker A; Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands., Meulenbeld HJ; Department of Internal Medicine, Gelre Ziekenhuizen, Zutphen, The Netherlands., Creemers GJ; Department of Internal Medicine, Catharina Ziekenhuis, Eindhoven, The Netherlands., van Weerden WM; Department of Urology, Erasmus MC, Rotterdam, The Netherlands., Jenster GW; Department of Urology, Erasmus MC, Rotterdam, The Netherlands., Nieuweboer AJM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., de Wit R; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Martens JWM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.; Department of Medical Oncology, Cancer Genomics Netherlands, Rotterdam, The Netherlands., Sleijfer S; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2019 Aug; Vol. 13 (8), pp. 1795-1807. Date of Electronic Publication: 2019 Jun 28.
DOI: 10.1002/1878-0261.12529
Abstrakt: 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.
(© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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