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

AR-V7 variants are resistant to arbiraterone, apalutamide, and enzalutamide^1,3,4

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