Expression of Androgen Receptor Splice Variant 7 or 9 in Whole Blood Does Not Predict Response to Androgen-Axis–targeting Agents in Metastatic Castration-resistant Prostate Cancer

Improved Androgen Receptor Splice Variant 7 Detection Using a Highly Sensitive Assay to Predict Resistance to Abiraterone or Enzalutamide in Metastatic Prostate Cancer Patients

“…Consequently, our present 56% AR-V7 detection rate with the highly sensitive assay appears to be higher than the AR-V7 positivity rates of 17.8-55% reported in prior studies that have also used real-time qPCR [11][12][13][14][15]20]. Our current results are in the upper range of the findings of studies that have used ddPCR to quantify AR-V7 expression in mCRPC patient-derived CTCs, whole blood, or exosomes, which have reported 18-66% rates of AR-V7 expression [22][23][24][25][26][27]. Notably, Tagawa et al [25] reported an AR-V7 detection rate of 66%, which is partly explained by the higher rates of previous ARSinhibitor use (42.6%) and of visceral metastases (40.7%), compared with those in our study (29.2% and 22%, respectively).…”

“…Over 90% of hsARV7patients exhibited PSA response and good survival outcomes. However, some AR-V7 + patients may also have had a PSA response following treatment with ARS inhibitors, as has been described previously [27,28]. For example, Bernemann et al [28] reported a series of four AR-V7 + patients who were treated with ARS inhibitors and exhibited a PSA decrease of >50%.…”

“…Several different blood-based AR-V7 detection assays are available, including CTC-based protein immunofluorescence and mRNA-based assays that can be performed using CTCs, whole-blood RNA, and plasma-derived exosomes [16,20]. Furthermore, different detection technologies are [11][12][13][14][15][21][22][23][24][25][26][27].…”

Regulation of ELL2 stability and polyubiquitination by EAF2 in prostate cancer cells

“…ELL2 depletion has previously been associated with splicing in plasma cells . AR splice variants have been reported to be frequently observed in castration‐resistant prostate cancer . We therefore investigated whether depletion of ELL2 could induce the expression of AR splice variants in C4‐2 cells.…”

“…18 AR splice variants have been reported to be frequently observed in castration-resistant prostate cancer. 19 We therefore investigated whether depletion of ELL2 could induce the expression of AR splice variants in C4-2 cells. Knockdown of ELL2 and/or EAF2 did not induced splicing in AR protein ( Figure 7B).…”