Title: Exploitation of extracellular vesicles for precision diagnostics of prostate cancer
Jesus MARTINEZ DE LA FUENTE (Spain) CIBER, Instituto de Salud Carlos III, Madrid
Guido JENSTER (The Netherlands) Erasmus Medical Center, Rotterdam
Alicia LLORENTE (Norway) Oslo University Hospital, The Norwegian Radium Hospital, Oslo
Aija LINĒ (Latvia) Latvian Biomedical Research and Study Centre, Riga
Asko URI (Estonia) University of Tartu, Tartu
In Europe, prostate cancer (PCa) is the most common male cancer affecting approximately 400,000 men annually. The development of sensitive and versatile non-invasive biomarker assays for differentiating between benign, indolent PCa and fast progressing PCa requiring aggressive treatment, represents the greatest unmet clinical need in the management of PCa.
PROSCANEXO is based on the hypothesis that the extracellular vesicles (EVs) count and in particular specific PCa-derived EV subpopulations are increased in biofluids of PCa patients, and that their RNA and protein content is specifically changed. EV quantification and qualitative molecular profiling can therefore be used for early PCa detection, monitoring the disease and distinguishing aggressive from indolent PCa. The molecular cargo of EVs, in particular specific miRNAs, long noncoding RNAs and proteins, reflects the molecular composition of cancer cells and predicts the presence and behavior of PCa cells.
The overall aim of PROSCANEXO is to establish technically and clinically validated noninvasive tools for PCa diagnosis and prognosis based on the analysis of EV counts and molecular cargo in patients’ biofluids.
This will be achieved through: (i) implementing a highly sensitive thermal transduction biosensor for the quantification of total and PCa-derived EVs in patients’ biofluids using a collection of specific probes for capturing EVs and profiling of protein kinase (PK) activity; (ii) employing assays for the quantification of RNA biomarkers in EVs isolated from biofluids; (iii) establishing a centralized PCa database and integration of the EV assays with current standard-of-care analyses for PCa early detection and prognosis. The assays will be validated using blood and urine samples of PCa patients selected from large, retrospective longitudinal PCa cohorts established by the project partners or available at their institutions.
PROSCANEXO is expected to establish an integrated non-invasive biomarker approach that, on top of the standard-of-care clinical parameters, utilizes changes in EV counts and molecular cargo to significantly improve diagnosis and prognosis of men with PCa. The employment of an ultrasensitive biosensor for the quantification of EVs will enable unbiased, rapid and inexpensive quantification of PCa-derived EVs and monitoring of EV dynamics during the course of the disease. The implementation of RNA biomarkers and PK activity profiling will strengthen the specificity of the integrated biomarker panels.
The PROSCANEXO biomarker panel is expected to prevent unnecessary diagnostic biopsies, reduce monitoring biopsies in active surveillance and avoid needless invasive therapeutic interventions. PROSCANEXO will therefore have a high impact for PCa patients, the health services and society.
PROSCANEXO has developed different sensing systems for the detection of prostate cancer patients. For this purpose, extracellular vesicles have been used as tumor markers and commercial antibodies, nanobodies specially developed for this project, as well as different RNAs specific to this type of cancer have been used. Different proofs of concept of these biosensors have been developed and they have been able to differentiate between pool of samples from healthy patients and patients with prostate cancer. Throughout the life of the project, progress has been made in the development of both thermal and luminometric lateral flow immunoassays for the quantification of these extracellular vesicles, either by direct quantification or by protein kinase quantification.
(Project funded under JTC 2016)