Researchers have developed a new imaging technique that can identify variants of the androgen receptors that do not respond to current androgen-deprivation therapies. The discovery could lead to better clinical management of patients with castration-resistant prostate cancer (CRPC).
Findings from the study, “An imaging agent to detect androgen receptor and its active splice variants in prostate cancer,” were published in JCI Insight.
Although androgen deprivation therapy often improves the outcome of prostate cancer patients, tumor cells eventually develop resistance to the therapy and evolve into castration-resistant prostate cancer. Tumor cells still depend on an active androgen receptor, but no longer respond to hormone therapies.
One mechanism by which cells acquire resistance is through the presence of active variants of the androgen receptor that do not include the portion of the receptor to which androgens and anti-androgen drugs bind. Because all current hormone therapies target the domain of the androgen receptor, or directly reduce androgen levels, the therapies do not work for patients with the variants.
This is particularly important because patients with specific variants, such as V7, are known to respond to taxanes. Knowing whether a patient has a specific variant may prevent patients from receiving futile, high-cost treatments, such as enzalutamide (Xtandi, $7,450 a month) and abiterone (Zytiga, $5,000 a month), and more personalized treatments.
Researchers led by Marianna Sadar developed new imaging compounds that bind to a particular region common to the androgen receptor and its variant forms. It allowed them to identify and target prostate cancer cells that still depend on the androgen receptor activity.
Using a technique known as single-photon emission computed tomography-computed tomography (SPECT/CT), the compounds were able to specifically detect prostate cancer cells expressing the androgen receptor in a mouse model of prostate cancer.
Although the compounds did not discriminate which androgen receptors lacked the ligand-binding domain, researchers suggest that it might be possible in the future with sequential and improved probes.
The team maintains that the findings already show significant potential for monitoring disease response to treatment — and may provide a means of targeted radiotherapy in the future.
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