Detecting PSMA in Prostate Cancer Noninvasively With Liquid Biopsy
Jacob E. Berchuck, MD, discussed research behind using a blood-based liquid biopsy in prostate cancer and findings presented at the 2024 ESMO Congress.
Jacob E. Berchuck, MD
A novel epigenetic liquid biopsy platform for determining tumor prostate-specific membrane antigen (PSMA) expression in patients with prostate cancer could bypass the need for PSMA PET scans, according to findings presented at the 2024 ESMO Congress.1
According to Jacob E. Berchuck, MD, the study sought to evaluate whether this tool could noninvasively detect tumor PSMA expression in patients with metastatic castration-resistant prostate cancer.
“I think what this epigenomic liquid biopsy platform potentially provides is a way, with a single blood draw, to profile several therapeutic targets for patients with advanced solid tumors to facilitate precision treatment,” explained Berchuck, assistant professor, Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, in an interview with Targeted OncologyTM.
In the interview, Berchuck further discussed this research behind using a blood-based liquid biopsy in prostate cancer and findings presented at the 2024 ESMO Congress.
Targeted Oncology: Can you discuss the background of this research presented at ESMO?
Berchuck: The objective of our study at ESMO was to evaluate whether a new epigenomic liquid biopsy tool could noninvasively detect tumor PSMA expression in [patients] with metastatic castration-resistant prostate cancer. Liquid biopsy tools focused on epigenomic profiling of tumor features in the blood have enabled some new capabilities that previous liquid biopsy tools focused on genomics were not able to do. We specifically sought to evaluate whether the new epigenomic liquid biopsy platform from Precede Biosciences could noninvasively detect tumor PSMA expression, and we correlated the tumor PSMA expression on PET scan with what we were able to observe in the blood using this liquid biopsy platform.
What are the main advantages of using a blood-based liquid biopsy over traditional PSMA PET scans?
I'll highlight 2 things. The first, which I think is really important, is access. The FDA label for Pluvicto [177Lu-PSMA-617]requires a PSMA PET scan to confirm tumor PSMA expression prior to patients receiving or being eligible to receive treatment. We know that PSMA PET scans are not available in some places in the United States and certainly globally, and so I think the opportunity, or the ability to assess tumor PSMA expression, in which patients are eligible for this FDA-approved, life-prolonging drug in other ways that are more accessible to communities, especially with underserved populations, is incredibly important, which we are hopeful that this liquid biopsy approach will be able to achieve.
The second is that, as I mentioned, PSMA PET scans, molecular imaging, are limited to a single target, so the implications there are that I am incredibly optimistic with all of the clinical trials going on in this space, that there are going to be FDA-approved drugs, 3, 4, or 5 years from now for [patients] with prostate cancer, but really all solid tumor types targeting an array of different targets. So, how are we going to, in the clinic, identify which patients tumors express which targets to prioritize specific treatments for individual patients to maximize response rates, [and] improve clinical outcomes while minimizing delivering treatments that are not going to be effective for individuals? So, I think what this epigenomic liquid biopsy platform potentially provides is a way with a single blood draw to profile several therapeutic targets for patients with advanced solid tumors to facilitate precision treatment.
With over 30 PSMA-targeting agents in development and the FDA-approved 177Lu-PSMA-617, how do you think this epigenomic platform could impact clinical decision-making?
There’s an incredible opportunity for liquid biopsies to really inform which patients should and shouldn’t receive PSMA-directed therapy in the clinic. I think it’s already important, given that we have an FDA-approved drug, [177Lu-PSMA-617] targeting PSMA. But as you mentioned, with the clinical development of many more PSMA-directed therapies, this is only going to become an increasingly important issue in the clinic.
Right now, we have the question: Is this patient going to benefit from [177Lu-PSMA-617]? There’s an incredible range in whether patients do or don’t respond. Some patients respond for a year, 18 months, or even 2 years, while other patients do not respond at all. I think using clinical biomarkers, like those we’re developing with this liquid biopsy platform, could really facilitate identifying which patients in the clinic are likely or unlikely to benefit from PSMA-directed therapy.
How might this new platform influence the accessibility of PSMA-based therapies, especially for patients who may not have easy access to PSMA PET scans?
We know that there are areas in certain communities where PSMA PET scans are not available. Since a PSMA PET scan is a prerequisite for receiving [177Lu-PSMA-617], this is a huge barrier. I think this is particularly important because these communities are often enriched for underserved patients. From an access and equity standpoint, we need to be better about ensuring that patients have access to life-prolonging, FDA-approved therapies.
What we are excited about is the potential to use liquid biopsies. This involves taking a single tube of peripheral blood from a patient that can be drawn in any clinic in the US or around the world, and being able to get the diagnostic information needed to know whether an individual’s tumors express PSMA. The current ESMO abstract focuses on that specific question: Can we detect PSMA expression? We showed that we are able to do this with pretty good accuracy.
But the next question we really want to answer is, can we predict [177Lu-PSMA-617] outcomes? I think having a blood test that is accessible to all communities that indicates whether a patient is eligible and likely to benefit from this drug would be incredibly impactful.
What challenges do you foresee in adopting this type of blood-based diagnostic technology in community oncology, and how could they be overcome?
One area I am excited about is the new wave of therapies like antibody-drug conjugates, radioligand therapies, bispecific antibodies, all of which target tumor-enriched cell surface proteins. I am optimistic that we will see several FDA approvals for drugs in prostate cancer and across solid tumors over the coming years. As those drugs are approved, we are left with a huge challenge of which drug to give which patient at which time. When I think about adoption of these blood-based technologies into practice, both in academic settings and in the community, this could help overcome that challenge, to deliver precision to by being able to noninvasively assay which patients express tumors, express which targets, to be able to deliver the treatments that we that we that are going to be more likely to be effective to improve outcomes for our patients.
How might it shape the future of precision medicine in prostate cancer beyond PSMA?
One aspect of this liquid biopsy approach is the ability to get genome wide data from a simple blood draw. What I mean by that is that with molecular imaging tests like PSMA PET scans, that is limited to looking at 1 tumor drug target. With liquid biopsy platforms, where we are profiling epigenomic features across the entire genome, we can potentially get readouts on all, or most or some tumor drug targets to not just look at PSMA response, but with a simple blood draw, be able to predict response to or tumor expression of PSMA. There are several other drug targets in prostate cancer that are under development. With a simple, single blood draw, being able to assay for an individual patient on a given day their expression of several drug targets could be an incredibly powerful opportunity to deliver precision medicine, not just for PSMA, but for all the drug targets that are under development for prostate cancer.
What excites you most about the potential for epigenomic profiling to transform personalized treatment strategies in prostate cancer?
Over the last 15 to 20 years, we have seen an incredible explosion of our understanding of the molecular drivers of cancer and subsequently targeted therapies, immunotherapies, radioligand therapies, antibody-drug conjugates, to target those therapeutic vulnerabilities to improve outcomes for our patients. Our understanding, though, over the last couple decades, has mostly been focused on understanding tumor genomic alterations, the epigenetic features that drive tumorigenesis and that mediate response and resistance to our treatments are relatively not as well understood. With the development of epigenomic liquid biopsies, the ability to profile tumor epigenomic features with a simple blood draw, I think this has incredible potential to unlock our understanding of tumor molecular features, specifically epigenomic features, to understand how the epigenome regulates response resistance to our therapies, to gain new insights into therapeutic vulnerabilities, develop the next generation of drugs tailor our treatments better for our patients with our existing drugs. I am excited about the potential power of this technology and these tools to advance how we treat our patients.
What are the key takeaways and future directions?
The data we presented was focused on the ability of this epigenomic liquid biopsy platform to detect PSMA expression and tumor PSMA expression moving forward. I think the ultimate realization of this biomarker is the ability to not only detect PSMA expression, but also predict which patients do and do not or are likely or unlikely to benefit from [177Lu-PSMA-617]. That work is underway. We have seen some exciting early results, and we are hoping later this fall that we are going to be able to release some data demonstrating that this epigenomic liquid biopsy platform is a potentially powerful tool to stratify which patients are likely or unlikely to respond to [177Lu-PSMA-617]. I think the implications are first focused on [177Lu-PSMA-617] for PSMA, but the sky's the limit with thinking about all the other drug targets and drugs that are under development for how we can deploy such epigenetic liquid biopsy tools to advance precision oncology.
