Detecting predictive androgen receptor modifications in circulating prostate cancer cells.

AR‐V7 in circulating tumor cells cluster as a predictive biomarker of abiraterone acetate and enzalutamide treatment in castration‐resistant prostate cancer patients

“…8 In addition, detection of AR-V7 is associated with more rapid disease progression and shorter survival in CRPC. [9][10][11][12] Several groups have reported that the number and characteristics of CTCs in cancer patients parallel tumor burden and response to therapy. [13][14][15] CTCs are generally thought to detach from primary or secondary tumors of patients with advanced cancer prior to detection in the circulation.…”

Performance comparison of two androgen receptor splice variant 7 (AR‐V7) detection methods

“…Antonarakis et al [10] showed that detection of AR-V7 mRNA in circulating tumour cells (CTC) of patients with mCRPC was associated with non-response to next-generation ADT. Several subsequent confirmatory studies followed [3,[12][13][14] and importantly the response rates to taxane-based chemotherapy showed no significant difference between AR-V7positive vs -negative patients with mCRPC [3,10,[12][13][14][15][16]. These findings collectively argue for AR-V7 as a potential treatment selection biomarker in the setting of mCRPC ( Fig.…”

“…To compare the performance of two mRNA-based AR-V7 assays [3,10,12], we used three independent approaches: (i) an in vivo comparison using cell lines with known AR-V7 status (specificity), (ii) sensitivity threshold determination using series dilution assays, and (iii) direct practical performance comparison in liquid biopsies from patients with castrationresistant prostatic adenocarcinoma (for inclusion criteria see Steinestel et al [3] structure. Both assays span the exon junction between exon 3 and cryptic exon 3 of AR resulting in AR-V7 mRNA.…”

“…Both AR-V7 assays are mRNA-based and have been independently developed and previously published [1,3,10,13,14,17]. Briefly, the 'Antonarakis assay' [10] refers to a SYBR green-based qPCR [1,[13][14][15][16], whereas the 'Steinestel assay' [3] refers to a TaqMan qPCR. The design is depicted in Fig.…”

Targeting the N-Terminal Domain of the Androgen Receptor: A New Approach for the Treatment of Advanced Prostate Cancer

“…Antiandrogen therapies are ineffective at inhibiting AR splice variants, because these target the LBD, which is truncated from the AR protein.The presence of AR splice variants, such as AR-V7 and AR-V 567es , has been correlated with both primary and acquired resistance to antiandrogens and has been linked to more rapid disease recurrence, poor prognosis, and shorter survival [8,[54][55][56]. Of these, AR-V7 may be the most important, has been implicated in resistance to abiraterone and enzalutamide in men with advanced prostate cancer [8,11,57,58], and may play a role in partial resistance to docetaxel as well [59].…”