Biomarker testing and targeted therapies for metastatic prostate cancer

The following questions and responses have been lightly edited for grammatical purposes.

1) Could you talk about your research on developing blood-based biomarkers and how that fits in the world of prostate cancer diagnosis and treatment?

As a medical oncologist, I specialize in these systemic treatments. The majority of the men that I see or the men who really need a medical oncologist the most are men with metastatic or advanced prostate cancer. For men with advanced prostate cancer, sometimes there’s a role for radiation, rarely surgery. Systemic therapies like hormone therapy, chemotherapy, and targeted therapies are really the backbone of treatment for advanced prostate cancer. The real unmet need here is personalizing treatment decisions for the individual in front of you. 

The issue we run into for men with advanced prostate cancer is that we don’t have good tools we can use in the clinic to prioritize or know which of the treatments are going to be the most effective for that individual. We use our experience, our intuition, clinical data, how much cancer there is, where it’s located, how aggressive–and we’re using a lot of data. We have a lot that we can pull from, but we need better biomarkers and tests that we can use in the clinic. Say I have these five treatments, which one of them is going to be the most effective for the individual in front of me, so I can prioritize that to maximize its effectiveness and minimize side effects? We want to minimize giving treatments that aren’t going to be effective and are just going to have side effects. Some of our treatments, like chemotherapy and even PARP inhibitors, can have side effects. 

My real passion is developing tools that can allow us to get the right treatment for the right patient at the right time. How do we do that? Genomics are really important. Historically, to do that, we stick a needle into the tumor and get a piece of that tumor tissue to send off to the lab and run all sorts of tests to look at the genome and which genes are expressed. There’s an incredibly exciting array of molecular features that we can look at that we’re starting to learn are associated with responding or not responding to certain treatments.

The really exciting development has been over the last 5-7 years. We can now study a lot of those things in the blood. We’ve learned that tumor cells shed DNA into the bloodstream. Through a routine blood draw in the clinic, we can sort of dissect what DNA in the bloodstream is coming from the cancer cells and then study the DNA, the genes that are being expressed, and the mutations just by looking at that blood sample that we collected. What I’m working on developing is blood-based tests that allow us to say, “John Smith, you’re going to respond best to this treatment, and we should prioritize Treatment A. Joe Schmo, you’re going to respond better to Treatment C. Treatment A actually would have been really toxic without a likelihood of benefit.” 

This is making its way into the clinic. Biomarkers like this have demonstrated that we can use them to identify which treatments are going to be effective for individuals and use them to tailor treatment. I firmly believe that five years from now, we will have an array of blood-based biomarkers, blood-based tests that we can draw at a routine lab with the PSA that we can then use to prioritize and select which treatments are going to be most effective for which individuals. It’s going to maximize responses, improve longevity, and minimize toxicity with the growing number of treatments that are being developed.

Another thing I do is participate and lead clinical trials of testing new treatments. As more and more treatments become available and are demonstrated to be effective in prostate cancer, the importance of these biomarkers and personalizing our treatment decisions is going to be more and more profound. It’s an area I’m super passionate about. I think we’re just starting to see the promise of it for patients. I think over the next 5-10 years, we’re going to see it totally transform how we’re able to deliver care to men with advanced prostate cancer.

2) Are there drugs or targeted therapies that you expect will show up in the next few years?

I’ll highlight a really tangible example, PSMA, which is a protein on the surface of prostate cancer cells. We talked about how we can use an imaging test to localize where cancer cells are based on where the PSMA is. The most recent FDA-approved drug targets that PSMA protein. Instead of an imaging agent, a company basically conjugated together an antibody, a way of localizing where the PSMA is. Instead of lighting it up so we can see it on a scan, it’s linked to a toxic radioactive particle. You can think about it like a smart bomb. You give it through the IV, it goes through the blood circulation, localizes to where the PSMA cells are, and then delivers a toxic radioactive particle directly to the cancer cells. This is a drug that’s called Pluvicto or lutetium PSMA. It was FDA-approved, I think two years ago. It’s a drug that we use routinely now that I’ve seen fantastic responses, remissions of well beyond a year in some patients. 

The reason I use this as an example is that this approach targets proteins on the surface of cancer cells and delivers a toxic molecule to kill cancer cells. There are several proteins we’ve now found in prostate cancer and other cancer types that we can target, so there are several [drugs] under development using a similar approach. PSMA is the first. There’s B7-H3, Trop-2, STEAP1, and I can go on. There are 5-10 really promising proteins that use a similar concept of basically using these proteins that are expressed on the prostate cancer cells to target a treatment and then deliver an effective radioactive or chemotherapy molecule directly to the cancer. It’s effective, and because you’re delivering it right to the cancer, it minimizes side effects and toxicity from the treatment.

I think we’re going to see, over the next 5-10 years, several drugs coming out targeting these different proteins on the cancer cell surface. This is true for prostate cancer and other cancers as well, and I think it could yield an incredible number of drug advances for men with advanced prostate cancer. The exciting thing is that we’re moving them earlier and earlier in our treatment. Right now, they’re mostly being studied in men with metastatic cancer. I think as we see that they’re safe and effective, we’ll move that march earlier and use biomarkers to figure out which men aren’t going to be cured upfront with our initial treatment, and then we can use these to intensify treatment. I think that sort of nicely marries how the new drugs we’re developing are going to improve outcomes and how we need the biomarkers to then figure out the best way to deliver them in a personalized fashion to optimize outcomes for men with prostate cancer.

Watch our full discussion with Dr. Berchuck in the Outcomes4Me app.

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