Close Search X

Oncotype DX AR-V7 NUCLEUS DETECT

Why Nuclear Detection?

The Oncotype DX AR-V7 Nucleus Detect test is the first and only nuclear-localized assay to identify patients who will not respond to androgen receptor (AR)-targeted therapy (like abiraterone (Zytiga®), enzalutamide (Xtandi®) andapalutamide (Erleada®)) and should receive chemotherapy or other therapies instead.1-5 By identifying AR-V7 protein in the nucleus of circulating tumor cells (CTCs), the AR-V7 Nucleus Detect test eliminates false positives and detects resistance to AR-targeted therapies with unparalleled specificity.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. The splice variant remains constitutively active, but it lacks the binding domain for androgens and AR-targeted therapies. Patients with nuclear AR-V7 protein receive no benefit from AR-targeted therapies, but may still respond to taxane chemotherapy.1,4

AR-V7 is a splice variant of the androgen receptor (AR) that lacks the ligand binding domain2
Ligand Image
AR-V7 variants are resistant to arbiraterone, apalutamide, and enzalutamide1,3,4

The percentage of patients with AR-V7 in the nucleus (nuclear AR-V7+ patients) increases with continued exposure to AR-targeted therapies2:

  • Roughly 1 in 5 patients (18%) are nuclear AR-V7+ after receiving one round of AR-targeted therapy.
  • Roughly 1 in 3 patients (31%) are nuclear AR-V7+ after receiving two rounds of AR-targeted 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 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

Nuclear Activity Image

REFERENCES

1. Antonarakis et al. N Engl J Med. 2014.
2. Scher et al. JAMA Oncol. 2016.
3. Scher et al. Eur Urol. 2016.
4. Antonarakis et al. JAMA Oncol. 2015.
5. Scher et al. JAMA Oncol. 2018.

 

Stay in Touch

Have a specific question? Want to keep up with our latest news? We're here for you.

 Contact Us
Copyright © 2004- Genomic Health, Inc. All Rights Reserved.
In the US and certain other jurisdictions, Genomic Health, Oncotype, Oncotype DX, Oncotype IQ, Breast Recurrence Score, Recurrence Score, DCIS score, Colon Recurrence Score Genomic Prostate Score, AR-V7 Nucleus Detect, Pass It On: Until Every Woman Knows, and Making Cancer Care Smarter are registered trademarks of Genomic Health, Inc.
Making cancer care smarter.™
X

We may use cookies to improve your experience with our website and to provide you with more relevant content based on your interests. To learn more about what information we collect, how we use it, and how to manage cookies, review our Privacy Policy.