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How to Detect ARV7 mRNA in PBMCs and CTCs to Predict Chemotherapy Response in Prostate Cancer

Speakers: Mercedes Marín-Aguilera, PhD, Research Fellow, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS)


Androgen receptor (AR) signaling is crucial for prostate cancer growth. Constitutively active AR splicing variants have been identified as an important mechanism of AR pathway activation in conditions of androgens depletion. The most studied splicing form is the variant 7 (ARV7), which lacks the AR ligand-binding domain and is constitutively activated in absence of androgens. Detected in circulating tumor cells (CTCs) or in whole blood, ARV7 has been previously associated with lower activity of some anti-androgens treatments. However, controversial studies exist about its role as a biomarker of chemotherapy response. We measured ARV7 mRNA in 92 peripheral blood mononuclear cells (PBMC) samples and in 24 CTC-enriched samples (obtained by IsoFlux technology) from patients prior to receiving chemotherapy. Gene expression was correlated with treatment response. As a result, we observed that high PBMC ARV7 mRNA levels correlated with better taxanes response and longer progression free survival (PFS) measured by the increase of PSA levels at serum. Conversely, high ARV7 expression in CTCs correlated with shorter radiological-PFS after chemotherapy treatment. In conclusion, ARV7 levels in PBMCs or CTCs have a different predictive role in chemotherapy response, suggesting a potential influence of AR pathway from PBMC in such response modulation.