Androgen receptor splice variant 7 mRNA (AR-V7 mRNA)

Androgen receptor splice variant 7 (AR-V7) is a truncated isoform of the androgen receptor that arises from the alternative splicing of AR pre-mRNA, specifically through the inclusion of cryptic exon 3. This structural alteration results in a protein that lacks the C-terminal ligand-binding domain but retains the N-terminal and DNA-binding domains, allowing it to function as a constitutively active transcription factor. AR-V7 is a primary driver of resistance to second-generation androgen receptor signaling inhibitors, such as enzalutamide and abiraterone, in patients with metastatic castration-resistant prostate cancer. Therapeutic strategies targeting the AR-V7 mRNA or pre-mRNA utilize antisense oligonucleotides (ASOs) to induce RNase H-mediated degradation of the transcript or splice-switching oligonucleotides to prevent the formation of the variant. Clinical candidates like AZD5312 (IONIS-AR-2.5Rx) have been developed to silence the expression of both full-length AR and its variants to overcome treatment resistance. The presence of AR-V7 mRNA in circulating tumor cells is a validated clinical biomarker used to predict poor response to hormonal therapies and guide the transition to taxane-based chemotherapy.

Other names

AR3Androgen receptor variant 7AR-V7AR-V7 transcriptAndrogen receptor splice variant 7

Antisense-mediated mRNA degradation via RNase H recruitment, splice-switching to inhibit cryptic exon inclusion, and N-terminal domain antagonism to block transcriptional activity.