Androgen Receptor (AR) and AR Splice Variants in Prostate Cancer

Section Editor: Trevor Flood MD FRCPC
May 27, 2026

The androgen receptor (AR) is a protein inside prostate cells that receives signals from male hormones called androgens, the most important of which is testosterone. These signals tell prostate cells to grow and divide. Almost all prostate cancers depend on this androgen signal to grow, which is why treatments that lower androgen levels or block the androgen receptor are the foundation of treatment for prostate cancer that has spread. Over time, however, some prostate cancers find ways to keep the androgen receptor switched on even when androgen levels are very low. One of these ways involves altered forms of the receptor called AR splice variants, the best known of which is AR-V7. Testing for the androgen receptor and AR-V7 can help explain how a cancer is behaving and guide the choice between different treatments.

This article explains what the androgen receptor is, what AR splice variants are, why testing is done, how the testing is performed, how results are reported, and what a result means for treatment.

What the androgen receptor does

The androgen receptor (AR) is a protein found inside prostate cells. Its job is to receive signals from androgens, a group of male hormones that includes testosterone. When an androgen enters the cell and binds to the androgen receptor, the receptor moves into the cell’s nucleus, the control center that holds the cell’s DNA, and switches on genes that tell the cell to grow and divide. In the normal prostate, this is a tightly controlled process.

In prostate cancer, this same process is hijacked. The cancer cells use androgen receptor signaling to fuel their own growth. This is the single most important fact about prostate cancer biology, and it is the reason that the androgen receptor is the central target of treatment for advanced disease. Treatments that interfere with this signal, by lowering the body’s androgen levels or by blocking the receptor itself, can slow or shrink the cancer.

Androgen receptor testing and what it shows

The androgen receptor (AR) is the protein inside prostate cells that receives growth signals from male hormones. Pathologists can test for the androgen receptor in tumor tissue using a laboratory technique called immunohistochemistry (IHC), in which a specially designed antibody attaches to the androgen receptor protein and produces a color change visible under the microscope. The color appears in the cell nucleus because that is where the androgen receptor does its work.

The large majority of prostate cancers are androgen receptor-positive, meaning the receptor is present. For this reason, AR testing by immunohistochemistry is not performed routinely on every prostate cancer the way it is for some other tumor types; the result is usually expected. AR testing is more often used in specific situations, for example, to help confirm that a cancer found at another site started in the prostate, or to study cancers that have lost typical prostate features. A separate and more clinically active area of testing does not assess whether the androgen receptor is present, but whether the cancer has developed altered forms of the receptor that resist treatment. That is the focus of the sections below.

What AR splice variants are

To understand AR splice variants, it helps to know how a cell builds a protein. The instructions for the androgen receptor are stored in a gene. To make the receptor protein, the cell first copies the gene into a working template called messenger RNA, then edits that template by cutting out unnecessary segments and joining the remaining pieces. This editing step is called splicing. Normally, splicing produces a complete, full-length androgen receptor.

An AR splice variant is a shortened version of the androgen receptor that results when splicing is carried out differently. The most important AR splice variant in prostate cancer is called AR-V7. In AR-V7, the part of the receptor that normally binds to androgens, called the ligand-binding domain, is missing. This is the key point: the part of the receptor that hormone-blocking drugs are designed to act on is the part that AR-V7 has lost.

Because AR-V7 has no site for androgen binding, it does not require androgens to be active. It stays switched on permanently, continuously telling the cancer cell to grow even when androgen levels in the body have been driven very low by treatment. AR-V7 is mostly found in advanced prostate cancer that has stopped responding to hormone-lowering treatment, and it is uncommon in early, untreated prostate cancer.

Why AR splice variant testing is done

Testing for AR splice variants, in practice almost always AR-V7, is done to help understand whether a prostate cancer is likely to resist a particular type of treatment. AR-V7 is a shortened form of the androgen receptor that stays active without needing male hormones, as explained above.

Advanced prostate cancer that continues to grow despite treatment that lowers testosterone is called castration-resistant prostate cancer. Two of the main drugs used in this setting are abiraterone and enzalutamide. Both work by targeting the androgen receptor signaling pathway: abiraterone further lowers androgen production, and enzalutamide blocks androgens from binding to the receptor. Both depend, in different ways, on the receptor’s hormone-binding region. Because AR-V7 is missing that region, a cancer driven by AR-V7 has a way to keep growing despite these drugs.

The clinical rationale for AR-V7 testing is as follows: if a cancer is positive for AR-V7, it is less likely to respond well to abiraterone or enzalutamide, and a different approach, such as taxane-based chemotherapy (e.g., docetaxel or cabazitaxel), may be more likely to help. Taxane chemotherapy acts through a distinct mechanism independent of the androgen receptor, and studies suggest it can remain effective in AR-V7-positive cancers. AR-V7 testing is one piece of information among several that an oncologist may weigh when choosing between these treatments.

How the test is performed

AR-V7 testing looks for a shortened, treatment-resistant form of the androgen receptor. It can be performed in two main ways.

Liquid biopsy (blood-based testing)

The most established way to test for AR-V7 uses a liquid biopsy, a test performed on a blood sample rather than on a piece of tissue. Advanced prostate cancers shed whole cancer cells into the bloodstream; these are called circulating tumor cells. A specialized laboratory captures these circulating tumor cells from the blood sample and tests them for AR-V7. Some tests detect the AR-V7 protein inside the nucleus of the captured cells, while others detect the AR-V7 messenger RNA, the working template described earlier. A liquid biopsy is convenient because it requires only a blood draw and can be repeated over time as the cancer changes.

Tissue-based testing

AR-V7 can also be tested on a tissue sample from a biopsy of the cancer, including biopsies taken from sites where the cancer has spread, such as bone or lymph nodes. Testing may be done by immunohistochemistry to detect the AR-V7 protein, or by methods that detect AR-V7 messenger RNA. Tissue testing is less commonly used than blood-based testing for this particular marker.

AR-V7 testing is specialized and is not available in every laboratory. It is generally used in the setting of advanced, castration-resistant prostate cancer rather than early-stage disease.

How results are reported

AR-V7 testing looks for a shortened form of the androgen receptor that is associated with resistance to certain hormone-blocking drugs. Results are usually reported in one of two ways.

AR-V7-positive (detected) — The AR-V7 variant was found in the circulating tumor cells or tissue tested. This indicates that the cancer carries a form of the androgen receptor that can stay active without male hormones, and that the cancer is less likely to respond well to abiraterone or enzalutamide.
AR-V7-negative (not detected) — The AR-V7 variant was not found in the sample tested. The cancer is more likely to retain a response to abiraterone or enzalutamide, although a negative result does not guarantee a response.

A report for a separate androgen receptor (AR) immunohistochemistry test, which simply asks whether the full-length receptor protein is present, will instead be described as AR-positive or AR-negative, with an estimate of how many tumor cells show staining. It is worth being clear that AR testing and AR-V7 testing answer different questions: AR testing asks whether the receptor is present at all, while AR-V7 testing asks whether the cancer has developed a specific treatment-resistant form of the receptor.

What the result means

AR-positive (standard androgen receptor testing)

Most prostate cancers are androgen receptor-positive, meaning the cancer cells contain the full-length androgen receptor protein. On its own, an AR-positive result is an expected finding in prostate cancer and confirms that the cancer’s biology is consistent with a tumor that arose in the prostate. It does not, by itself, predict how the cancer will respond to any particular drug. Loss of androgen receptor staining is less common and can be seen in certain unusual or treatment-altered prostate cancers; your pathologist and oncologist will interpret this in the context of the overall findings.

AR-V7-positive

An AR-V7-positive result means the cancer carries a shortened form of the androgen receptor that stays active without male hormones. In a patient with castration-resistant prostate cancer (cancer that has continued to grow despite treatment that lowers testosterone), this result is associated with a lower likelihood of benefit from the AR-targeted drugs abiraterone and enzalutamide. It may prompt the oncologist to consider taxane-based chemotherapy, which acts through a mechanism independent of the androgen receptor, as a treatment that can remain effective in AR-V7-positive disease. AR-V7 status is one of several factors, including prior treatments, overall health, symptoms, and other test results, that contribute to the treatment decision.

AR-V7-negative

An AR-V7-negative result means the specific AR-V7 variant was not detected. A cancer that is AR-V7-negative is more likely to retain a response to abiraterone or enzalutamide than an AR-V7-positive cancer. However, a negative result does not guarantee that these drugs will be effective, because resistance to AR-targeted therapy can develop through mechanisms that this test does not measure.

Important limitations of AR-V7 testing

AR-V7 is a shortened, treatment-resistant form of the androgen receptor, and testing for it can provide useful information, but the test has real limitations that are important to understand.

AR-V7 status can change over the course of the disease. A cancer that is AR-V7-negative at one point may become AR-V7-positive later, particularly after further treatment, which is one reason blood-based testing that can be repeated is attractive. Results can also differ between laboratories, because different tests detect AR-V7 in different ways (protein versus messenger RNA, and in circulating tumor cells versus tissue) and there is no single universal standard. A negative result does not rule out resistance to hormone-blocking therapy, since resistance has many possible causes. For these reasons, AR-V7 testing is not used as a routine test for every patient with prostate cancer. It is best understood as one additional piece of information, used in specific situations in advanced disease, rather than as a test that decides treatment on its own. Your oncologist is the right person to explain whether AR-V7 testing is appropriate in your situation and how to interpret the result alongside everything else known about your cancer.

What happens next

The steps that follow depend on which test was done and what it showed.

If your report mentions androgen receptor (AR) testing, the result is most often AR-positive, which is an expected finding in prostate cancer. This result confirms the cancer’s biology but does not by itself decide treatment. If you are unsure why AR testing was done, your pathologist or oncologist can explain its purpose in your specific case.
If your cancer is castration-resistant and AR-V7 testing was performed, your oncologist will use the result, together with your prior treatments and overall situation, to help choose between AR-targeted drugs such as abiraterone and enzalutamide and taxane-based chemotherapy.
If AR-V7 testing has not been done but you have questions about resistance to hormone-blocking therapy, it is reasonable to ask your oncologist whether AR-V7 testing is available and whether it would add useful information in your case.

If you are waiting for results, or have received a result you do not yet fully understand, it is entirely appropriate to ask your oncologist or pathologist to explain what was found and what it means for your situation.

Questions to ask your doctor

Did my pathology report include androgen receptor (AR) testing, and what did it show?
Has my cancer become castration-resistant, meaning it is growing despite treatment that lowers testosterone?
Would AR-V7 testing add useful information in my situation, and is it available to me?
If AR-V7 testing is done, would it be performed on a blood sample or on tissue?
If my cancer is AR-V7-positive, how would that affect the choice between abiraterone, enzalutamide, and chemotherapy?
If my cancer is AR-V7-negative, how confident can we be that hormone-blocking therapy will work?
Could my AR-V7 status change over time, and might the test be repeated later?
What other factors are you considering when choosing my next treatment?
Are there clinical trials relevant to my situation that involve the androgen receptor or AR splice variants?

The information on this page is intended for general informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the guidance of your physician or other qualified health provider with any questions you may have regarding your medical condition.