CTC-derived AR-V7 detection as a prognostic and predictive biomarker in advanced prostate cancer

Abstract

Introduction: Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay has been identified as one of the markers that can be used to predict surv<ival, with added value beyond currently available prognostic factors. Recently, androgen receptor splice variant 7 (AR-V7) detection has been associated with worse outcomes for patients with castration-resistant prostate cancer (CRPC) treated with novel androgen receptor-signaling (ARS) inhibitors such as abiraterone and enzalutamide but not taxane chemotherapies. Areas covered: In this manuscript, the authors review the available biomarkers in CRPC and discuss emerging data on the value of CTC-derived AR-V7 status to assess prognosis and its potential role to guide treatment selection for patients with advanced prostate cancer. Expert Commentary: Current evidence supports AR-V7 status as a prognostic biomarker and also as a potential predictive biomarker for patients with mCRPC. The authors expect that the incorporation of AR-V7 status and other biomarkers (e.g. AR mutations) in the sequential assessment of patients with advanced prostate cancer will lead to a more rational use of available and future therapies, with significant improvements in outcomes for our patients.

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

“…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].…”

“…These findings suggest that AR-V7 may serve as a predictive biomarker of the lack of response to ARS inhibitors. The prevalence of AR-V7 in men with mCRPC increases with increasing lines of treatment and depends on the assay used [16]. Furthermore, the impact of minimal AR-V7 expression on clinical outcomes following ARS-inhibitor treatment remains unclear.…”

Roles of Splicing Factors in Hormone-Related Cancer Progression

“…Moreover, AR-V7-positive CTCs are associated with worse PSA response rates and shorter progression-free and overall survival rates. Therefore, AR-V7 may be promising for a potential target of diagnosis, prognosis and therapy in metastatic CRPC [69][70][71]. The full-length AR protein is encoded by AR isoform composed of eight exons and consists of four core domains: The N-terminal domain (NTD), the DNA binding domain (DBD), the hinge region and the C-terminal ligand binding domain (LBD).…”

OTUB1&nbsp;Promotes Progression and Proliferation of Prostate Cancer via Deubiquitinating and Stabling Cyclin E1

“…However, many patients of PCa were diagnosed at a very late stage and their survival rate reduced drastically, due to no obvious symptoms apart from those of urinary tract infection (2). Currently the main and standard treatment is androgen deprivation therapy (ADT) because of the irreplaceable role of androgen receptor (AR) in progression of PCa (3,4). ADT mainly include medical castration and surgical castration, but most patients nally progressed to castration-resistant prostate cancer (CRPC), even metastasis castration resistant prostate cancer (mCRPC) with no effective treatment (5,6).…”