Mark Stein, MD, medical oncologist, Rutgers Cancer Institute of New Jersey, discusses androgen receptor (AR)—resistance in prostate cancer.

One lingering question in this space is whether or not these splice variants always exist at low levels in prostate cancer. According to Stein, the answer is that the splice variants are, indeed, always there, but it is not completely understood as to why they are there. The full-length AR is the majority of the androgen receptor in the cell, but not all of it, he explains. Under selective pressure, cells proliferate that are able to adapt to the presence of an AR-inhibitor, such as enzalutamide (Xtandi).

Stein says it is also interesting that, if a patient is given another treatment after an AR-inhibitor, such as chemotherapy, one can actually see the levels of the AR variants decreasing, suggesting that, once the selective pressure is removed, that variant goes away.

More remaining questions about AR—resistance in prostate cancer will soon be answered as novel biomarkers are embedded into future clinical trials.

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Mark Stein, MD, medical oncologist, Rutgers Cancer Institute of New Jersey, discusses androgen receptor–resistance in prostate cancer.

Dr. Stein on AR-Resistance in Prostate Cancer

Mark Stein, MD, medical oncologist, Rutgers Cancer Institute of New Jersey, discusses commercial tests for determining therapies for patients with prostate cancer.

Certain tests are helpful when understanding some of the more challenging clinical situations, explains Stein. It is not something that is routinely done, due to different insurance funds. However, it is effective during certain cases, in regards to determining which therapy a patient should receive.

Technology and platforms are developing quickly, making it necessary for physicians to remain updated on the ongoing trials in order to decide the most beneficial treatment for a patient. For instance, explains Stein, there might be trials looking at a particular biomarker, which could be an important way to determine which trials to enroll patients on.

Dr. Stein on Commercial Tests to Determine Therapies for Prostate Cancer

Mark Stein, MD, medical oncologist, Rutgers Cancer Institute of New Jersey, discusses trials investigating the use of circulating tumor cells as biomarkers for patients with prostate cancer.

Stein explains that these types of trials typically look to assess patients' survival. However, this can take a very long time, and it can slow trials down significantly. Thus, as an alternative, investigators have been looking at decreases in circulating tumor cells as a clinical endpoint in a trial to see if that varaible is correlated with survival in any way.

One such trial, says Stein, retrospectively showed that this decrease in circulating tumor cells can, indeed, be used as a surrogate. Additional studies with circulating tumor cells embedded into the trial design are now planned to definitively establish that those changes can be used as a surrogate for overall survival, and therefore expedite trial development.

Another exciting area of development has been utilizing changes in the androgen receptor to understand if tumors will still respond to hormonal therapies. Specifically, drugs such as enzalutamide (Xtandi) or abiraterone acetate (Zytiga) have become routine parts of practice with castration-resistant prostate cancer.

What has been shown thus far is that cells with a mutation in the androgen receptor do not appear to respond to hormonal therapy. According to Stein, this information is important to know up front, and it could also be an important mechanism of resistance.

Dr. Stein on Trials Investigating Biomarkers in Prostate Cancer

Mark Stein, MD, medical oncologist, Rutgers Cancer Institute of New Jersey, discusses the use of novel circulating biomarkers in the treatment of patients with prostate cancer.

The use of these biomarkers is considered to be an emerging concept, according to Stein, as they are not routinely used in current clinical care. However, Stein believes these advances in technology, including the ability to sample cells, blood, and DNA in circulation, will all soon be integrated into routine care in the coming months and years.

Oncologists strive to figure out which patients will benefit most from a specific agent, and also why certain drugs may stop working for particular patients. These lingering questions are the basis for the rationale behind the development of such circulating biomarkers.

Moreover, the rationale is to ultimately understand prognostic factors in prostate cancer. For example, if a patient has a lot of circulating tumor cells, that feature is typically considered to be a poor prognostic factor, says Stein. Conversely, if the amount of circulating tumor cells can be decreased, patients seem to subsequently achieve good responses to treatment.

Overall, these more novel biomarkers do, in fact, add something to the more traditional markers, like CAT scans or prostate-specific antigen testing, according to Stein.

Mark Stein, MD

Articles

Dr. Stein on AR-Resistance in Prostate Cancer

Dr. Stein on Commercial Tests to Determine Therapies for Prostate Cancer

Dr. Stein on Trials Investigating Biomarkers in Prostate Cancer

Dr. Stein on Circulating Biomarkers in Prostate Cancer