Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer

Bernemann, Christof; Schnoeller, Thomas; Luedeke, Manuel; Steinestel, Konrad; Boegemann, Martin; Schrader, Andres Jan; Steinestel, Julie

doi:10.1016/j.eururo.2016.07.021

Cited by 120 publications

(97 citation statements)

References 11 publications

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“…15 Taken together, the results suggested that AR-V7 status could be used to guide the choice of treatment in men with progressive mCRPC in need of a change in therapy. A series of reports followed, using a range of AR-V7 assays in smaller cohorts, some refuting 16 and others confirming, 17 albeit to variable degrees, but none used OS as the primary outcome measure. Missing from several reports were the details of the analytical performance of the assay itself, and in particular the demonstration that it was “fit-for-purpose” of using the reported result to support a clinical validation effort.…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer

et al. 2018

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Importance A blood test to determine whether to treat patients with metastatic castration-resistant prostate cancer (mCRPC) with an androgen receptor signaling (ARS) inhibitor or taxane is an unmet medical need. Objective To determine whether a validated assay for androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells (CTCs) that is localized to the nucleus can predict differential overall survival (OS) in mCRPC patients treated with taxanes vs. ARS inhibitors. Design Blinded correlative study. Patients were followed up to 4.3 years. Setting Multi-institution outpatient clinics at Memorial Sloan Kettering Cancer Center (USA), Institute for Cancer Research (UK) and London Health Sciences Centre (Canada). Participants A cross-sectional cohort of 248 patients with mCRPC drawn prior to 286 drug exposures were considered. The analysis subset included 142 patients drawn prior to administration of ARS inhibitors or taxanes at the second or greater line of systemic therapy for progressing mCRPC. Main Outcome(s) and Measure(s) OS following an ARS inhibitor or taxane in relation to pretherapy AR-V7 status. Results For mCRPC patients designated as high-risk by conventional prognostic factors, AR-V7-positive patients treated with taxanes have superior OS relative to those treated with ARS inhibitors, and AR-V7-negative patients treated with ARS inhibitors have superior OS relative to taxane-treated patients. Conclusion and Relevance Nuclear-localized AR-V7 protein in CTCs can identify patients who may live longer on taxane chemotherapy than on ARS inhibitors (abiraterone, enzalutamide, apalutamide).

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Section: Introductionmentioning

confidence: 99%

Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer

et al. 2018

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“…Castration-resistant prostate cancer (CRPC), previously known as hormone-refractory prostate cancer, is now understood to be a progressive of disease despite medical or surgical castration. [4][5][6] Castration resistance has historically been defined as progression despite achieving a castrate serum testosterone level lower than 50 ng/mL, which does not respond to ADT. Even though abiraterone acetate, enzalutamide, Ra-223 dichloride, and chemotherapy can be used for CRPC therapy, drug resistance often manifests in CRPC patients, and the overall survival benefit is limited.…”

Section: Introductionmentioning

confidence: 99%

Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

Wang

Yang

Zhou

et al. 2017

IJN

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“…Importantly, as the efficacy of chemotherapy appears to be independent of AR-V7 expression in CTCs and tissues, AR-V7 can potentially be used to guide patient therapy (Antonarakis et al 2015, Onstenk et al 2015, Scher et al 2016, an idea that is now being tested in multiple clinical trials (e.g., NCT02429193, NCT02269982, NCT02853097 and NCT02491411). Although the outcomes of these trials are eagerly awaited, it must be noted that exceptions have already been reported: a recent study found that AR-V7 status in CTCs cannot entirely predict non-response to abiraterone or enzalutamide (Bernemann et al 2016). Given that effective alternative treatment options are still somewhat limited, this latter study raises a note of caution for clinicians.…”

Section: Ar Splice Variantsmentioning

confidence: 87%

Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence

Coutinho¹,

Day²,

Tilley³

et al. 2016

Endocrine-Related Cancer

151

122

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The androgen receptor (AR) signaling axis drives all stages of prostate cancer, including the lethal, drug-resistant form of the disease termed castration-resistant prostate cancer (CRPC), which arises after failure of androgen deprivation therapy (ADT). Persistent AR activity in spite of ADT and the second-generation AR-targeting agents enzalutamide and abiraterone is achieved in many cases by direct alterations to the AR signaling axis. Herein, we provide a detailed description of how such alterations contribute to the development and progression of CRPC. Aspects of this broad and ever-evolving field specifically addressed in this review include: the etiology and significance of increased AR expression; the frequency and role of gain-of-function mutations in the AR gene; the function of constitutively active, truncated forms of the AR termed AR variants and the clinical relevance of alterations to the activity and expression of AR coregulators. Additionally, we examine the novel therapeutic strategies to inhibit these classes of therapy resistance mechanisms, with an emphasis on emerging agents that act in a manner distinct from the current ligand-centric approaches. Throughout, we discuss how the central role of AR in prostate cancer and the constant evolution of the AR signaling axis during disease progression represent archetypes of two key concepts in oncology, oncogene addiction and therapy-mediated selection pressure.

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Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer

Cited by 120 publications

References 11 publications

Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer

Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer

Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence

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