Androgen receptor messenger RNA (AR mRNA)

The Androgen receptor (AR) messenger RNA (mRNA) and its precursor (pre-mRNA) are the primary transcripts of the AR gene, serving as the essential templates for the synthesis of the AR protein. The AR protein is a nuclear transcription factor that mediates the biological effects of androgens and is a critical driver in the development and progression of prostate cancer. In advanced disease states like castration-resistant prostate cancer (CRPC), the AR transcript often undergoes alternative splicing to produce variants such as AR-V7, which lack the ligand-binding domain and remain constitutively active despite androgen deprivation therapy. Targeting the AR at the mRNA level using antisense oligonucleotides (ASOs) or RNA interference (RNAi) provides a therapeutic advantage by depleting both full-length and splice-variant proteins, thereby overcoming resistance to traditional AR antagonists. Experimental drugs like AZD5312 (Danvatirsen) utilize antisense technology to bind the AR mRNA and induce its degradation via RNase H, effectively silencing the AR signaling axis. This approach aims to halt tumor growth and induce apoptosis in cancer cells that have become independent of exogenous androgens. However, the clinical application of these therapies must address challenges such as delivery efficiency and potential class-related toxicities like hepatotoxicity and thrombocytopenia.

Other names

Androgen receptor mRNAAndrogen receptor pre-mRNAAR transcriptNR3C4 mRNAAndrogen receptor messenger RNA

Antisense oligonucleotides (ASOs) bind to the target mRNA or pre-mRNA to induce RNase H-mediated degradation or modulate splicing, while RNA interference (RNAi) uses siRNAs to trigger the RNA-induced silencing complex (RISC) for mRNA cleavage, both resulting in the depletion of the Androgen receptor protein.