Scientist hand holding test tube with blood in laboratory for liquid biopsy.
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Researchers at the Vall d’Hebron Institute of Oncology (VHIO) in Belgium, have developed a novel liquid biopsy methodology that enables the monitoring of disease evolution in patients with metastatic prostate cancer.

The study, published in Cancer Cell, leverages the RNA contained in extracellular vesicles shed by tumor cells into the bloodstream to capture the cancer’s genomic and transcriptomic evolution, offering a promising new tool for personalized cancer treatment.

Led by Joaquin Mateo, head of the Prostate Cancer Translational Research Group at VHIO, the study demonstrates how this liquid biopsy-based approach can detect tumor gene expression through RNA in circulating extracellular vesicles. According to the researchers, these findings could predict treatment response, identify mechanisms of drug resistance, and provide new avenues for studying cancer through non-invasive methods.

“Our findings open avenues for biomarkers of therapy response and acquired drug resistance to help guide clinical decisions in individual patients with metastatic prostate cancer throughout the course of disease,” said Mateo, also a Medical Oncologist at the Vall d’Hebron University Hospital.

Prostate cancer, the second most frequent cancer worldwide and the fifth leading cause of cancer death among men, has seen advancements in treatments and early detection. However, metastatic prostate cancer remains a significant challenge due to the heterogeneous response to treatments and the eventual development of drug resistance.

Extracellular vesicles, which naturally facilitate intercellular communication, carry proteins, lipids, metabolites, RNA, and DNA. These vesicles, when produced by tumor cells, play a crucial role in cancer progression and metastasis. However, their potential as a source of clinically relevant DNA and RNA biomarkers has been largely unexplored until now.

Irene Casanova, associate investigator in Mateo’s group and first author of the study, explained, “We have now developed a new liquid biopsy application for the analysis of circulating vesicles secreted by cancer cells and performed multi-omic profiling for the genomic and transcriptomic characterization of these tumors.”

The researchers analyzed liquid biopsies from a cohort of 53 patients with metastatic castration-resistant prostate cancer, who had received hormone therapy or chemotherapy. They found that the extracellular vesicles contained tumor-derived genetic material, allowing for the identification of specific mutations and the forecasting of disease evolution.

This technique enables the monitoring of on-therapy changes in tumors by analyzing mRNA expression in extracellular vesicles, which is protected from rapid degradation, thus providing clinically relevant information.

The study, conducted in collaboration with the Principe Felipe Research Institute (CIPF) in Valencia and the Spanish National Cancer Research Center (CNIO) in Madrid, highlights the transcriptomic profile of tumors that could serve as biomarkers of response or resistance to therapy. These findings could significantly expand the opportunities for studying cancer through minimally invasive liquid biopsies.

“Drug resistance remains a major challenge in more effectively treating cancer. Adaptive mechanisms of resistance occur more rapidly and dynamically than mutations driving acquired resistance. Monitoring these changes as they occur by liquid biopsy will enable real‐time clinical decision‐making and the selection of adaptive treatments to help combat evolving tumor dynamics earlier,” concluded Mateo.

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