AR splice variants in circulating tumor cells of patients with castration‐resistant prostate cancer: relation with outcome to cabazitaxel
2019
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 ARV9-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.
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