ARV7 is a modified version of the androgen receptor (AR), a protein found in cells. It arises from a process called alternative splicing of the androgen receptor gene, resulting in a shorter, altered protein. Its presence and function are significant in managing certain health conditions.
Understanding ARV7
ARV7 is a “splice variant” of the androgen receptor (AR) gene, meaning it is a naturally occurring, shorter version of the full-length AR protein. The androgen receptor is a type of protein that plays a central role in regulating cell growth and function, especially within male reproductive tissues. Normally, the full-length androgen receptor requires androgen hormones, such as testosterone, to bind to it for activation. This binding initiates a series of events that influence gene expression and cell activity.
In contrast, ARV7 is distinct because it lacks the part of the receptor where androgen hormones typically bind, known as the ligand-binding domain. Despite this missing domain, ARV7 can remain active and capable of signaling cell growth and division even in the absence of androgen hormones. This characteristic allows ARV7 to promote cell proliferation through its own unique transcriptional program, which can be different from the full-length AR. The ability of ARV7 to function independently of androgen binding is a defining feature that contributes to its role in various biological processes and certain disease states.
ARV7’s Impact in Prostate Cancer
ARV7 plays a significant role in prostate cancer, particularly concerning resistance to hormone therapies. Androgen deprivation therapy (ADT) and newer-generation anti-androgens are standard treatments for prostate cancer, aiming to reduce androgen levels or block the androgen receptor to slow cancer growth. However, many prostate cancers eventually develop resistance to these treatments, leading to disease progression.
ARV7 contributes to this resistance by enabling cancer cells to continue growing even when androgen levels are low or when full-length AR is blocked. Its presence can signify a more aggressive form of the disease, as patients with detectable ARV7 often experience shorter progression-free survival and overall survival when treated with androgen receptor signaling inhibitors. The emergence of ARV7 often occurs after initial hormone therapy, suggesting it is an adaptive mechanism that allows cancer cells to evade treatment and continue to grow.
Detecting ARV7 and Treatment Considerations
Detecting ARV7 is becoming an important aspect of personalized medicine in prostate cancer. One common method for detection involves liquid biopsies, which are blood tests that can identify cancer-related biomarkers. Specifically, ARV7 can be detected in circulating tumor cells (CTCs) found in the blood.
A positive ARV7 test result can significantly influence treatment decisions for prostate cancer patients. For individuals with metastatic castration-resistant prostate cancer (mCRPC), the presence of ARV7 often indicates that new-generation hormone therapies like abiraterone or enzalutamide may be less effective. In such cases, oncologists may consider alternative treatments, such as chemotherapy, which has shown benefit in ARV7-positive patients, or novel agents that target ARV7 directly or indirectly. Integrating ARV7 testing into clinical practice helps guide treatment choices.