Effective August 2, 2022, mdxhealth has acquired the Oncotype DX Genomic Prostate Score (GPS) test from Exact Sciences. Additionally, Genomic Health Inc, part of Exact Sciences, will continue to perform the GPS test during the transition. Further communications explaining transition plans will be provided in the coming months. For more details, please review the press release.
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Region: United States
Prostate Cancer

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