New liquid biopsy technique enables continuous analysis of metastatic prostate cancer and precise treatment planning.

Researchers from the Vall d’Hebron Oncology Institute (VHIO), part of Vall d’Hebron, have demonstrated in a study published in the journal Cancer Cell that the genetic material (DNA and RNA) present in extracellular vesicles derived from the tumor circulating in the blood of patients with metastatic prostate cancer reflects the genomic and transcriptomic characteristics of the patient’s tumor.

According to the Spanish Society of Medical Oncology (SEOM), prostate cancer is the second most common cancer in Spain and the most common among men, with an estimated 30,000 new cases in 2024. Today, most of these cancers are detected at an early stage and can be cured with surgery, radiotherapy or brachytherapy, with or without hormonal therapy. However, a proportion of these tumors eventually develop metastases or appear from the start. In these cases, hormonal treatment or chemotherapy may be effective initially, but over time the tumor adapts. Tools to monitor this tumor adaptation are needed

select the optimal treatment for each patient at each stage of the disease.

In this sense, the new study “opens the way to identifying biomarkers to analyze treatment response and the acquisition of resistance, and thus making the most appropriate clinical decisions at each stage of the disease,” he said. Joaquin Mateo, medical oncologist at the Vall d’Hebron University Hospital, head of the VHIO Prostate Cancer Translational Research Group and senior author of this study.

Circulating extracellular vesicles

Extracellular vesicles are particles secreted by cells under normal conditions to communicate with other cells in the body. These vesicles are highly heterogeneous and their contents are highly diverse, including DNA, RNA, lipids, and proteins. In the context of cancer, extracellular vesicles produced by tumor cells act as tumor scoutslooking for new places to expand. They play a crucial role in tumor progression, immune regulation and metastasis.

“However, the potential of tumor extracellular vesicles as a source of relevant DNA and RNA biomarkers remains largely unexplored,” he said. Irene Casanova, associate research fellow in the Prostate Cancer Translational Research Group and first author of this paper

“Our work aims to develop a new liquid biopsy application that will enable the analysis of circulating extracellular vesicles and, using a multiomics approach, perform genomic and transcriptomic characterization of the tumor.”

Tumor genomic and transcriptomic profiling

By analyzing serial plasma samples from 53 patients with metastatic prostate cancer who were undergoing hormonal therapy or chemotherapy, the researchers examined circulating DNA as well as DNA and RNA contained in extracellular vesicles. This analysis confirms that extracellular vesicles contain genetic material derived from the tumor

which makes it possible to identify mutations present in tumor cells and predict which tumors will have the worst evolution.

“In this sense, we confirm that we can use liquid biopsy of extracellular vesicles “with the same purpose as other sources of tumor DNA that we obtain from liquid biopsy, such as circulating tumor DNA or circulating tumor cells, but with the advantage that we can also track changes in genetic expression from RNA, which gives us an indication of what the tumor is like at that moment,” Casanova explained.

Using tumor mRNA encapsulated in circulating extracellular vesicles, researchers were able to minimally invasively identify: Tumor transcriptome profile as a biomarker of response and resistance. This allows us to learn which genes the tumor expresses at different times during the disease and to detect the adaptive changes that tumor cells make to become resistant to treatment. “These changes occur quickly and are more dynamic than the acquisition of resistance mutations, so being able to monitor them will allow us to make early clinical decisions and potentially change treatment before the patient becomes symptomatic if biopsy analysis shows that the tumor is already adapting. One of the main goals of precision medicine is to anticipate tumor evolution,” concluded Joaquin Mateo.

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