Beyond imaging: How blood-based biomarkers could refine prostate cancer treatment

For patients with advanced prostate cancer, treatment decisions are often made with incomplete information - leaving uncertainty about which therapies will work best.

New therapies like 177Lu-PSMA-617, a targeted radioligand therapy, have transformed care for metastatic disease, offering new hope where options were once limited.  But one challenge remains: it doesn’t work the same way for everyone.  Some patients respond well, while others see limited or no benefit, and clinicians don’t yet have reliable ways to predict who will fall into each group.

That uncertainty is driving a shift in how researchers think about cancer care.

Looking beyond imaging

As targeted therapies become more common, the need for better prediction tools has become increasingly urgent.  Today, clinicians rely heavily on imaging and standard blood markers to guide decisions, but these approaches don’t fully capture the complexity of a patient’s disease.

Researchers are now exploring new ways to understand tumor biology - approaches that go beyond what can be seen on a scan.

One promising direction is the use of liquid biopsy, a method that analyzes tumor-related material circulating in the blood.

A closer look at what tumors leave behind

In a recent study published in Cell Reports Medicine, researchers with the Masonic Cancer Center, University of Minnesota examined a specific component of liquid biopsy called extracellular vesicles.

These microscopic particles, often described as tiny packages released by cells, carry proteins and other molecular signals from their cell of origin.  In cancer, tumor cells shed these vesicles into the bloodstream, offering a window into disease activity without the need for invasive procedures and tissue biopsies.

By analyzing blood samples from 100 patients with metastatic castration-resistant prostate cancer— a form of advanced prostate cancer that has stopped responding to initial hormonal treatments —the research team used advanced mass spectrometry techniques to identify and measure tumor-derived proteins contained inside these vesicles.

What they found

The results revealed a remarkably detailed picture of tumor biology from a simple blood test.

Researchers identified more than 5,000 proteins in patient samples, including several that were strongly associated with clinical outcomes.  Proteins such as PSMA, B7-H3, Trop-2, and STEAP1 were linked to poorer survival, and their presence in the blood closely reflected the extent of cancer in the body. Conversely, other proteins were associated with longer survival.Some of these proteins are also being explored as targets for emerging therapies, suggesting potential future applications.

Taken together, these findings suggest that blood-based protein signals could provide meaningful insights into how aggressive a patient’s cancer is, and how it may respond to certain treatments.

Why it matters

For clinicians, this kind of information could help reduce uncertainty in treatment decisions.

Rather than relying solely on imaging or broad clinical indicators, blood-based biomarkers could offer a more dynamic and personalized view of the cancer .  This has the potential to improve patient selection for therapies like Lu-PSMA-617, ensuring that the right patients receive the right treatment at the right time.

Equally important, the approach is minimally invasive, making it easier to monitor disease over time using serial blood collections

This approach gives us a new way to understand what the prostate cancer  is doing and how patients may respond to treatment,’ said Dr. Ali T. Arafa, a postdoctoral researcher at the Masonic Cancer Center in the Department of Pharmacology and the lead author of the study.  “It allows us to capture important biological signals through a simple blood test.”

Dr. Emmanuel Antonarakis, the senior author of the study and Associate Director of Translation at the Masonic Cancer Center add: “While many cancer blood tests  have focused on DNA-based analysis, this work highlights the potential of studying tumor-derived proteins in the blood, which can give additional information,”

A collaborative effort

The study reflects collaboration across multiple programs and departments at the University of Minnesota and the Masonic Cancer Center.

It also highlights the role of shared research infrastructure, particularly the Analytical Biochemistry Shared Resource, whose mass spectrometry capabilities enabled the depth and scale of the proteomic analysis.

What comes next

While the findings are promising, further research is needed before these biomarkers can be used in routine clinical care.

Future studies will focus on confirming these results in larger and more diverse patient populations, as well as integrating these approaches into clinical trials.  The goal is to move toward a more precise, biology-driven model of cancer care, one that reduces uncertainty and improves outcomes for patients with advanced prostate cancer and other malignancies.