New Liquid Biopsy Method for Metastatic Prostate Cancer

• The results of the study conducted by VHIO were published in the journal cancer cell, show that a new liquid biopsy-based method can monitor tumor gene expression via RNA contained in circulating extracellular vesicles secreted by cancer cells..
• These findings may help predict treatment response, facilitate the development of new combination strategies to combat acquired drug resistance mechanisms, and expand the ability to study cancer using liquid biopsy..

Researchers from the Vall d’Hebron Oncology Institute (VHIO), which is part of the Vall d’Hebron, demonstrate in a study published in the journal Cancer cell what material (DNA and RNA) contained in extracellular vesicles of tumor origin circulating in the bloodstream of patients with metastatic prostate cancer, reflects the genomic and transcriptomic characteristics of the patient’s tumor.

Extracellular vesicles secreted by tumor cells into the bloodstream contain tumor-derived material that could be used as a biomarker of response and/or resistance to treatment in patients with metastatic prostate cancer. Cancer cell The researchers describe how they developed A new liquid biopsy-based tool for monitoring tumor gene expression from mRNA contained in extracellular vesicles derived from the tumor.

This biomarker may help predict response to treatment and the development of new combination therapies that can reverse the resistance mechanisms that tumor cells acquire during treatment.

This research was made possible thanks to funding from the la Caixa Foundation, the FERO Foundation and the CRIS Foundation against Cancer.

“The results of the study open the possibility of identifying biomarkers to analyze the response to treatment and the acquisition of resistance, and thus make the most appropriate clinical decisions at each stage of the disease,” explains Dr. Joaquin Mateo, a medical oncologist at the University of Vallée Hospital d’Hebron, head of the VHIO Prostate Cancer Translational Research Group and senior author of the study.

New treatment strategies for patients with refractory metastatic prostate cancer

According to SEOM, prostate cancer is the second most diagnosed cancer in Spain, first among men, with an estimated 30,000 new cases in 2024. Currently, the vast majority of cases are diagnosed at early stages and are curable through surgery, radiotherapy or brachytherapy, with or without hormonal therapy.

However, a proportion of these tumors eventually metastasize or metastasize from the start. In these cases, using hormonal treatment or chemotherapy may be effective, but eventually the tumor adapts. Tools to monitor this tumor adaptation can help choose the best treatment for each patient at each stage of the disease.

Extracellular vesicles are particles that cells secrete under normal conditions to communicate with other cells in the body. These vesicles are very heterogeneous and their contents are very diverse: DNA, RNA, lipids, proteins…

In the context of cancer, extracellular vesicles produced by tumor cells act as tumor scouts in search of new sites for further expansion and play a key 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,” says Dr. Irene Casanova, a 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 tumor characterization.”

Tumor genomic and transcriptomic profiling

Using serial plasma samples from 53 patients with metastatic prostate cancer who were receiving hormonal therapy or chemotherapy, the researchers analyzed circulating DNA and the DNA and RNA contained in extracellular vesicles. This analysis confirms that extracellular vesicles contain tumor-derived genetic material, information from which allows us to learn about the mutations present in tumor cells and which tumors will have the worst evolution.

“In this sense, we have confirmed that we can use liquid biopsy of extracellular vesicles for 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 ‘monitor changes in genetic expression based on RNA, which tells us what the tumor looks like at a given moment,’” explains Dr. Casanova.

In this work, the authors analyzed tumor messenger RNA (mRNA) in circulating plasma vesicles for the first time. “This is a source of information about the tumor that has not been amenable to liquid biopsy until now, since mRNA in the blood is easily destroyed. On the other hand, the mRNA that we find in vesicles is protected and retains information,” says the researcher.

With this tumor mRNA encapsulated in circulating extracellular vesicles, the researchers were able to minimally invasively identify the tumor transcriptome profile as a biomarker of response and resistance. That is, we can know what genes the tumor expresses at different stages of the disease and identify adaptive changes what tumor cells do to adapt and become resistant to treatment.

“These changes occur rapidly 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 liquid biopsy analysis shows that the tumor is already adapting. One of the main goals of precision medicine is to anticipate tumor evolution,” concludes Dr. Joaquin Mateo.

The study was published in the journal Cancer cell collaborated with researchers from the Prince Felipe Research Centre (CIPF) in Valencia and the National Centre for Cancer Research (CNIO) in Madrid.

This study was funded by a Junior Leadership Fellowship awarded by the La Caixa Foundation to Dr. Irene Casanova and a FERO-Ramon Areces Fellowship for the project “New Liquid Biopsy Approaches in Prostate Cancer to Inform Precision Medicine” awarded to Dr. Joaquin Mateo. The VHIO Prostate Cancer Translational Research Group also benefits from the support of the CRIS Foundation to Fight Cancer.

Research Article: Irene Casanova-Salas et al. Circulating tumor-derived extracellular vesicles for monitoring metastatic prostate cancer genomics and transcriptome evolution. Cancer Cell 42, 1-13. July 8 https://doi.org/10.1016/j.ccell.2024.06.003

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