The AR-V7 Nucleus Detect® test reduces false positives and detects resistance to AR-targeted therapies.4
How AR-V7 causes resistance to AR-targeted therapies
Tumors can adapt (and become resistant) to AR-targeted treatments. One of the most common adaptations is AR-V7—a protein variant of the androgen receptor. This splice variant is constitutively active and it lacks the ligand-binding domain, which is critical for the effectiveness of AR-targeted therapies. Patients with nuclear AR-V7 protein receive no benefit from AR-targeted therapies but may still respond to taxane chemotherapy.1-5
AR-V7 is a splice variant of the androgen receptor (AR) that lacks the ligand-binding domain2
The percentage of patients with AR-V7 in the nucleus (nuclear AR-V7+ patients) increases with exposure to multiple therapies, including AR-targeted therapies1:
- Roughly 1 in 5 patients (18%) are nuclear AR-V7+ after receiving two rounds of therapy
- Roughly 1 in 3 patients (31%) are nuclear AR-V7+ after receiving three or more rounds of therapy
Why nuclear localization eliminates false positives
The AR-V7 Nucleus Detect test detects protein in the nucleus of circulating tumor cells (not cytoplasmic AR-V7)—making it more specific than assays that do not localize AR-V7 identification. Studies show that AR-V7 protein found in the nucleus of circulating tumor cells (CTCs) is an absolute indicator of resistance. Although AR-V7 proteins are also found in the cytoplasm, transcription of tumor growth genes occurs in the nucleus.3 In addition, some AR-V7 protein does not translocate to the nucleus, and some mRNA does not translate into protein.3 As a result, nuclear localization of the AR-V7 protein is important to avoid the potential for false positives.
- Cytoplasmic AR-V7 translocates into the nucleus
- Nuclear AR-V7 binds to DNA
- Transcription of tumor growth genes
- Translation of tumor-growth gene mRNA into protein
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