In contrast, there is no relationship between presence of AR-V7 and response to chemotherapy—in this case, docetaxel or cabazitaxel (Jevtana). What we have shown is that the survival of patients is improved in patients with AR-V7 present who receive a taxane, and it is inferior for those who receive AR-directed therapy.
It is very important to understand that the splice variant is in the nucleus where it binds to DNA and functions, in order to be very specific to the test results. If AR-V7 is present, then we know that these are patients who should not be treated with an AR-directed drug. This was 1 experience that we published earlier this year, now it is going through a validation process to confirm that this is true.
In this particular case, we are trying to predict and identify what biologic feature in this patient’s case will predict for response or nonresponse of a particular drug.
It sounds like there are a lot of developments taking place with regard to biomarkers.
When you think about it, you can actually look at a patient’s blood and you can see the cells that are very homogenous and look very similar. Those are tumors that tend to respond to a targeted agent—particularly those who are more advanced. It looks as if you are treating 20 cancers at once.
But recently the focus is the heterogeneity—how chaotic does it look? The earlier in the course it is, the less chaotic it is. As it moves down the road in second- and third-line settings, it gets much more heterogeneous. That’s where you can make the argument that a cytotoxic or biologic agent may be preferable. Those are the types of questions being asked.
Liquid biopsies have been discussed in great detail this year. What role do you see them having in prostate cancer?
In lung cancer, there were 2 liquid biopsy tests approved as companion tests. These are tests for CTC DNA, which are looking for a specific mutation. In prostate cancer, the numbers of mutations that clearly predict for sensitivity are fewer. It’s harder to identify the types of changes that are predictive using CTC DNA, even though the technology is improving very quickly.
Research has shown that they can see if there is overexpression or amplification of the AR, which is turning out to be a predictor of nonresponse. Now, the assays have to get to the point of establishing analytical validity, which means they are done at a performance level that’s consistent anywhere the assay is done.
In many cases, that’s almost harder to do to get to that level of performance than it is to develop the drug. The whole field of companion diagnostics is really where the field is headed.
Ideally, you would like to be able to do a blood test and say, “This is the drug for you.” You want to be able to monitor the change over time in a tumor to understand when a drug should be added to what patients are already getting versus changing therapy completely.
What do you believe the field can accomplish in the next 5 years?
I would like to be part of the accomplishment. In his Cancer Moonshot program, Vice President Joe Biden is looking for 10 years of progress in 5 years. I am totally optimistic that it can be achieved.
We recently met in Washington, DC, as a group—the Blood Profiling Atlas—with the enthusiasm of the assay developers and regulatory agencies. The spirit of collaboration is just incredible. There is importance to sharing information so things can go forward.