Role of AR-V7 in Multidisciplinary Prostate Cancer Care

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With the varied treatment approaches available for patients at different stages of prostate cancer, multidisciplinary care is more important than ever, according to Charles J. Ryan, MD. The vast majority of patients with prostate cancer will be under the care of a medical oncologist and a urologist, as well as a urological surgeon and a radiation oncology. Even with the diagnosis of prostate cancer, patients will continue to need urologic care. While collaborating with an oncologist is common and appropriate, many urologists are able to administer newer hormonal agents for prostate cancer, explains Ryan.

Progress continues in the search for predictive markers for prostate cancer. While there is no predictive marker that can be considered “standard of care,” one of the most promising markers is the androgen receptor variant 7 (AR-V7). Patients with tumors harboring AR-V7 have a preponderance of androgen receptors that are able to actively signal without the presence of androgen. Based on the biology of this variant, androgen synthesis inhibitors and androgen receptor antagonists would be of very little value to these patients, since signalling occurs even without androgen.

While this biomarker has been found to have predictive value, evaluation is still continuing and is not readily available through the community clinician’s office. Currently, testing requires the presence of circulating tumor cells, along with special processing and interpretation. Furthermore, Ryan adds, the exact relationship between AR-V7 and androgen receptor amplification and standard androgen receptor signaling or the presence of standard androgen receptors remains unclear. While such a marker can aid in predicting who will not benefit from newer hormonal therapies, the field is in need of a marker that is predictive of response to agents. Identifying a reliable predictive marker will be useful in terms of saving time, saving money, and avoiding disappointment, notes Ryan.

At this time, the prevailing thinking is that AR-V7 is likely to emerge as a predominant signaling force as the cancer progresses. Still, it has been detected even in patients with localized disease, who are undergoing localized therapy. The more important question, Ryan suggests, is, “What is the ratio of AR-V7 to standard androgen receptor over time as the disease evolves?”

When the standard androgen receptor is blocked by drugs or androgen deprivation therapy, it may allow the outgrowth of tumors that harbor the AR-V7 variant, explains Ryan. Once AR-V7 is present in the tumor and becomes the predominant signaling force, it will likely remain a signaling force throughout progression of the cancer. Thus, if a patient has AR-V7 and is unable to receive enzalutamide or a similar drug, he would likely not become more responsive to the drug at a later stage. However, one idea being explored is whether or not chemotherapy, for example, might diminish or eliminate some of those subpopulations of tumor cells that harbor AR-V7, making the tumor then susceptible to enzalutamide or abiraterone.