What is the Origin of Androgen Receptor Splice Variants?

The concept emerged from molecular oncology and genetics research as scientists investigated mechanisms of therapeutic resistance in prostate cancer. The most studied variant, AR-V7, was identified as a driver of resistance to standard hormonal therapies. This molecular phenomenon represents an adaptation by cancer cells to bypass androgen deprivation strategies.

What is the Mechanism of Androgen Receptor Splice Variants?

Due to the absence of the LBD, splice variants like AR-V7 become constitutively active, meaning they can translocate to the nucleus and activate gene transcription without binding to an androgen ligand such as testosterone or dihydrotestosterone. This bypass mechanism renders the cancer cell resistant to drugs like enzalutamide and abiraterone, which target the LBD of the full-length receptor. The detection of these variants acts as a predictive biomarker for clinical treatment failure.

Androgen Receptor Splice Variants

Meaning

Androgen receptor splice variants are truncated protein isoforms of the full-length androgen receptor (AR) that arise from alternative splicing of the AR gene. These variants often lack the C-terminal ligand-binding domain (LBD) of the full receptor structure. Their presence is a critical clinical finding, particularly in the context of advanced prostate cancer.

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How Does Testosterone Replacement Therapy Affect Prostate Cancer Risk?

The relationship between testosterone therapy and prostate cancer is governed by a saturation model, ensuring safety in screened men.

∞ Testosterone Therapy
∞ Saturation Model
∞ Low Testosterone

HRTioJuly 31, 2025

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Can Personalized Hormone Protocols Mitigate Resistance in Prostate Cancer?

Personalized hormonal protocols can mitigate prostate cancer resistance by exploiting the cancer's own adaptations as therapeutic targets.

∞ PSA Response
∞ Castration-Resistant Prostate Cancer
∞ AR-V7

HRTioJuly 25, 2025

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What Are the Clinical Implications of Androgen Receptor Splice Variants in Prostate Cancer?

Androgen receptor variants are cellular adaptations driving treatment resistance, making their detection a key guide for personalizing prostate cancer therapy.

∞ Alternative Splicing
∞ Androgen Deprivation
∞ Androgen Receptor

HRTioJuly 25, 2025

Androgen Receptor Splice Variants

Meaning

Origin

Mechanism

How Does Testosterone Replacement Therapy Affect Prostate Cancer Risk?

Can Personalized Hormone Protocols Mitigate Resistance in Prostate Cancer?

What Are the Clinical Implications of Androgen Receptor Splice Variants in Prostate Cancer?

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