Why AR-V7 Nuclear Detect?

The Oncotype DX AR-V7 Nucleus Detect® test is a nuclear-localized assay to identify patients who may not respond to androgen receptor (AR)-targeted therapy (such as abiraterone, enzalutamide, and apalutamide) and should receive chemotherapy or other therapies instead.1-4

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.

  1. Cytoplasmic AR-V7 translocates into the nucleus
  2. Nuclear AR-V7 binds to DNA
  3. Transcription of tumor growth genes
  4. Translation of tumor-growth gene mRNA into protein