Multi-analyte liquid biopsy to monitor tumor genomic evolution and therapy response in advanced Prostate Cancer: MultiLQB-PC

Programme(s):

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Topic(s): MSCA-IF-2020 - Individual Fellowships

Call for proposal: H2020-MSCA-IF-2020

Funding Scheme: MSCA-IF-EF-RI - RI – Reintegration panel

Grant agreement ID: 101025901

Project description

An exosome-based liquid biopsy for prostate cancer

Exosomes are small vesicles secreted by the majority of eukaryotic cells and contain proteins, DNA and other biomolecules. Emerging evidence indicates that cancer cells also secrete exosomes which can be exploited as an approach for cancer diagnosis. MultiLQB-PC is an EU-funded project that aims to develop a liquid biopsy-based approach for the non-invasive diagnosis of prostate cancer. Researchers will integrate the detection of circulating tumour DNA and circulating tumour cells with exosomes to generate a sensitive assay for monitoring the progression of metastatic prostate cancer. MultiLQB-PC is expected to also aid disease prognosis and patient stratification and identify drug resistance cases.

Objective

Metastatic prostate cancer (mPC) is a lethal disease. Androgen deprivation therapy is the mainstay of patient care. In addition, DNA repair defects is a novel therapeutic target in mPC. However, resistances invariably arise, triggered most of the times by tumor genomic evolution. Liquid biopsy has emerged as a tool to non-invasively profile tumor genomics over time. Beyond circulating tumor DNA (ctDNA) and circulating tumor cells (CTC), small extracellular vesicles, known as exosomes, have been identified to contain tumor genomic material. Over the last years, I have developed a method to pursue analysis of tumor genomic material from exosomes at a very low cost. The analysis of exoDNA/RNA is a promising tool that represents a new non-invasive, sensitive and very informative new method for PC monitoring.

In this project, I aim to integrate the genomic analysis of exoDNA/RNA together with ctDNA and CTCs in advanced PC to:
1) Identify prognostic signatures for clinically-relevant patient stratification;
2) Define circulating predictive signatures of drug response/resistance; and
3) Validate biomarkers of therapy response for selection of subsequent lines of treatment.

Therefore, this fellowship would allow me to take a significant step towards the implementation of this new technology in the study of mPC genomics and mechanisms of response/resistance to novel targeted drugs. Furthermore, I will be able to integrate my research into clinical trials and, ultimately, impact personalized patient care.