New Liquid Biopsy Method Enables Monitoring of Disease Evolution in Metastatic Prostate Cancer Patients

by Roman Kasianov       News

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A new liquid biopsy approach enables monitoring of disease evolution in patients with metastatic prostate cancer through the analysis of extracellular vesicles (EVs) in the bloodstream. These vesicles, which contain tumor-derived material, can serve as biomarkers for therapy response and resistance.

This research, led by the Vall d’Hebron Institute of Oncology (VHIO) and published in Cancer Cell, highlights a notable advance in understanding and treating metastatic prostate cancer.

Prostate cancer remains the second most common cancer and the fifth leading cause of cancer death among men globally, with an estimated 1.5 million new cases and 397,000 deaths in 2022. Advances in treatment and early detection have reduced mortality rates in many high-income countries since the mid-1990s. Early-stage prostate cancer is often curable through surgery, radiotherapy, or brachytherapy, with or without hormone therapy. However, metastatic prostate cancer poses significant treatment challenges due to its heterogeneous response to therapy and the eventual development of drug resistance.

VHIO prostate cancer translational research group

Study Overview

The study, directed by Joaquin Mateo, Head of VHIO’s Prostate Cancer Translational Research Group, investigates the DNA and RNA material contained in circulating EVs secreted by tumor cells. These vesicles capture the genomic and transcriptomic evolution of the cancer in patients with metastatic prostate cancer. Mateo emphasizes that these findings provide a new method for identifying biomarkers of therapy response and resistance, which could guide clinical decisions throughout the disease progression.

Extracellular Vesicles as Biomarkers

Extracellular vesicles are known to mediate various biological processes and facilitate intercellular communication. These particles contain proteins, lipids, metabolites, RNA, and DNA, playing a key role in tumor progression, immune regulation, and metastasis. The potential of tumor-derived EVs as sources of clinically relevant DNA and RNA biomarkers has not been extensively explored until now.

The research team developed a liquid biopsy application to analyze circulating vesicles secreted by cancer cells. They conducted multi-omic profiling to characterize the genomic and transcriptomic features of metastatic prostate cancer. This approach was validated through a retrospective study involving 53 patients with metastatic castration-resistant prostate cancer undergoing hormone therapy or chemotherapy.

Findings and Implications

The analysis of DNA and RNA in circulating EVs confirmed that these vesicles contain tumor-derived genetic material. This enables the identification of specific mutations and provides insights into the disease's evolution. The study demonstrated that mRNA encapsulated in circulating EVs is protected from degradation, making it a reliable source of clinically relevant information.

This research was conducted in collaboration with the Principe Felipe Research Institute (CIPF) in Valencia and the Spanish National Cancer Research Center (CNIO) in Madrid. The findings expand opportunities for studying cancer through minimally invasive liquid biopsies. Monitoring changes in transcriptomic features via liquid biopsy can facilitate real-time clinical decision-making and adaptive treatment strategies to combat evolving tumor dynamics.

Future Directions

This study underscores the importance of developing new tools and identifying biomarkers of response and resistance to guide and adapt treatment strategies for metastatic prostate cancer. The ability to monitor tumor evolution in individual patients offers a promising approach to improving personalized treatment outcomes.

This work received funding from the ”la Caixa” Foundation, FERO Foundation, and CRIS Cancer Foundation, supporting VHIO’s Prostate Cancer Translational Research Group in their efforts to advance cancer research and treatment.

References:

  1. Casanova-Salas, I., et al. Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution. Cancer Cell. July 8, 2024. DOI: 10.1016/j.ccell.2024.06.003.
  2. Bray, F., et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263.

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