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Last update 08 May 2025

AR-V7 positive Castration-Resistant Prostatic Cancer

Last update 08 May 2025

Basic Info

Synonyms-

Introduction-

Drugs associated with AR-V7 positive Castration-Resistant Prostatic Cancer

Cabazitaxel Acetone

Target

Tubulin

Mechanism

Tubulin inhibitors

Active Org.

Aventis Pharma Ltd. [+12]

Originator Org.

Sanofi

Active Indication

Prostatic Cancer [+9]

Inactive Indication

Adenocarcinoma of Esophagus [+29]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

United States

First Approval Date17 Jun 2010

Clinical Trials associated with AR-V7 positive Castration-Resistant Prostatic Cancer

NCT02621190

/ WithdrawnPhase 2IIT

Non-randomized Phase 2 Open-label Multicenter Study Determining the Response to Cabazitaxel in Metastatic Prostate Cancer (mCRPC) Patients With AR-V7 Positive Circulating Tumor Cells (CTCs): CARVE

After failure on docetaxel, which has been the standard first line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC), several treatment options are currently available. In retrospective studies, resistance has been described to two of the treatment options, enzalutamide and abiraterone, when a splice variant of the Androgen Receptor (AR-V7) is present on circulating tumor cells (CTCs). The investigators hypothesize that patients with AR-V7 positive CTCs do have a meaningful response to cabazitaxel.

Start Date01 Feb 2016

Sponsor / Collaborator

Erasmus MC

[+1]

100 Clinical Results associated with AR-V7 positive Castration-Resistant Prostatic Cancer

100 Translational Medicine associated with AR-V7 positive Castration-Resistant Prostatic Cancer

0 Patents (Medical) associated with AR-V7 positive Castration-Resistant Prostatic Cancer

Literatures (Medical) associated with AR-V7 positive Castration-Resistant Prostatic Cancer

01 Dec 2022·European Journal of Cancer

CABA-V7: a prospective biomarker selected trial of cabazitaxel treatment in AR-V7 positive prostate cancer patients

Article

Author: Haberkorn, Brigitte C M ; Mathijssen, Ron H J ; Lolkema, Martijn P ; de Wit, Ronald ; Isebia, Khrystany T ; Helmijr, Jean C A ; van IJcken, Wilfred F J ; Kraan, Jaco ; Helgason, Helgi H ; Van, Mai N ; Brouwer, Rutger W W ; van den Hout-van Vroonhoven, Mirjam C G N ; Buck, Stefan A J ; Martens, John W M ; Beaufort, Corine M ; Hamberg, Paul ; Oole, Edwin ; Oomen-de Hoop, Esther ; Mostert, Bianca ; Sleijfer, Stefan ; Jansen, Maurice P H M ; van Riet, Job ; Sieuwerts, Anieta M ; Belderbos, Bodine P S

BACKGROUNDMetastatic castration-resistant prostate cancer (mCRPC) patients with positive AR-V7 expression in their circulating tumour cells (CTCs) rarely derive benefit from abiraterone and enzalutamide.DESIGNWe performed a prospective, multicenter, single arm phase II clinical trial (CABA-V7) in mCRPC patients previously treated with docetaxel and androgen deprivation therapy.OBJECTIVEIn this trial, we investigated whether cabazitaxel treatment resulted in clinically meaningful PSA response rates in patients with positive CTC-based AR-V7 expression and collected liquid biopsies for genomic profiling.RESULTSCabazitaxel was found to be modestly effective, with only 12% of these patients obtaining a PSA response. Genomic profiling revealed that CTC-based AR-V7 expression was not associated with other known mCRPC-associated alterations. CTC-based AR-V7 status and dichotomised CTC counts were observed as independent prognostic markers at baseline.CONCLUSIONSAR-V7 positivity predicted poor overall survival (OS). However, cabazitaxel-treated AR-V7 positive patients and those lacking AR-V7 positivity, who received cabazitaxel as standard of care, appeared to have similar OS. Therefore, despite the low response rate, cabazitaxel may still be an effective treatment in this poor prognosis, AR-V7 positive patient population.

01 Oct 2022·Advanced Science

De Novo Design of an Androgen Receptor DNA Binding Domain‐Targeted peptide PROTAC for Prostate Cancer Therapy

Article

Author: Xu, Shan ; Ma, Jian ; Gao, Yang ; Jian, Yanlin ; Fan, Yizeng ; Chen, Yule ; Liu, Donghua ; Li, Lei ; Wang, Zixi ; Wei, Yi ; Zhang, Dize ; Ma, Bohan

AbstractAndrogen receptor splice variant‐7 (AR‐V7), one of the major driving factors, is the most attractive drug target in castration‐resistant prostate cancer (CRPC). Currently, no available drugs efficiently target AR‐V7 in clinical practice. The DNA binding domain (DBD) is indispensable for the transcriptional activity of AR full length and AR splice variants, including AR‐V7. Based on the homodimerization structure of the AR DBD, a novel peptide‐based proteolysis‐targeting chimera (PROTAC) drug is designed to induce AR and AR‐V7 degradation in a DBD and MDM2‐dependent manner, without showing any activity on other hormone receptors. To overcome the short half‐life and poor cell penetrability of peptide PROTAC drugs, an ultrasmall gold (Au)‐peptide complex platform to deliver the AR DBD PROTAC in vivo is developed. The obtained Au‐AR pep‐PROTAC effectively degrades AR and AR‐V7 in prostate cancer cell lines, particularly in CWR22Rv1 cells with DC50 values 48.8 and 79.2 nM, respectively. Au‐AR pep‐PROTAC results in suppression of AR levels and induces tumor regression in both enzalutamide sensitive and resistant prostate cancer animal models. Further optimization of the Au‐AR pep‐PROTAC can ultimately lead to a new therapy for AR‐V7‐positive CRPC.

10 Mar 2022·OncogeneQ1 · MEDICINE

Targeting a splicing-mediated drug resistance mechanism in prostate cancer by inhibiting transcriptional regulation by PKCβ1

Q1 · MEDICINE

Article

Author: Nguyen, Hao G ; Hann, Byron ; Gordan, John D ; Steri, Veronica ; Hwang, Y Christina ; Melnyk, James E ; Shokat, Kevan M ; Feng, Felix Y

AbstractThe androgen receptor (AR) is a central driver of aggressive prostate cancer. After initial treatment with androgen receptor signaling inhibitors (ARSi), reactivation of AR signaling leads to resistance. Alternative splicing of AR mRNA yields the AR-V7 splice variant, which is currently an undruggable mechanism of ARSi resistance: AR-V7 lacks a ligand binding domain, where hormones and anti-androgen antagonists act, but still activates AR signaling. We reveal PKCβ as a druggable regulator of transcription and splicing at the AR genomic locus. We identify a clinical PKCβ inhibitor in combination with an FDA-approved anti-androgen as an approach for repressing AR genomic locus expression, including expression of AR-V7, while antagonizing full-length AR. PKCβ inhibition reduces total AR gene expression, thus reducing AR-V7 protein levels and sensitizing prostate cancer cells to current anti-androgen therapies. We demonstrate that this combination may be a viable therapeutic strategy for AR-V7-positive prostate cancer.

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AR-V7 positive Castration-Resistant Prostatic Cancer

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