Final Report Summary - PROSENSE (Cancer Diagnosis: Parallel Sensing of Prostate Cancer Biomarkers)
Prostate cancer (PCa) is the most commonly diagnosed and the leading cause of mortality among Western men. Although a majority of prostate cancer patients are diagnosed with curable, organ confined disease, more than a quarter of them experience a relapse within 5 years after surgery due to its heterogeneous character. Furthermore, the majority of prostate tumours are detected at early stages with uncertain prognosis.
Hence, we need to set out to identify early predictive markers of prostate cancer that can be integrated with reliable and robust sensing platforms, which may be useful for early diagnosis as well as to predict the clinical outcome and treatment response.
The Marie Curie Initial Training Network PROSENSE (2012-2016) aimed at meeting the major challenges in the development of diagnostic tools for prostate cancer by training a new generation of young scientists in multidisciplinary techniques and methods.
PROSENSE was a coordinated research training network involving academic, industrial and clinical partners. PROSENSE was a unique programme bringing together training across disciplines and across sectors, complemented by researcher career development tools.
PROSENSE was a coordinated research training network involving university groups, R&D sections of small and medium enterprises, research institutes, hospitals and the R&D section of a large enterprise from the biomedical field.
The scientific aspects of PROSENSE were centred around the themes of:
• Development and study of biomarkers
• Detection techniques development
• Probe immobilisation and characterisation
• System integration and validation
A full programme of cross-disciplinary and cross-sectoral secondments, training and events enabled PROSENSE to promote interaction, knowledge exchange and collaboration in the multidisciplinary field of biosensor design with the aim of developing improved devices for prostate cancer diagnosis, prognosis and treatments.
It improved sensitivity, selectivity, robustness and speed of biosensing technologies for the simultaneous screening of biomarkers; developed lab-on-a-chip devices requiring minute amounts of clinical samples and increase likelihood of viable fit-for-purpose prostate cancer biosensing products.
Work on the different scientific work packages has been progressed with a number of significant results. PSA was used as a test biomarker for the development of the majority of the sensors, since this marker is currently the gold standard in PCa diagnosis (even though it is not a very reliable marker). However, most of the techniques can be adapted for other markers present in blood or urine.
A few of the sensors developed are singleplex, i.e. they measure only one marker at a time. An example is the inexpensive lateral flow devices for PSA and for PSA glycosylation as well as the optical chemiluminesce sensors in a microfluidic device and the magnetic bead-based electrochemical sensors.
The majority of the sensors however can be explored in a multiplex system, i.e. platforms that can be expanded to measure a panel of biomarkers at the same time. These include:
• DNA aptamer based electrochemical sensors for PSA, AMACR, HER2, PSA glycosylation
• Use of field-effect transistors with aptamers or hybrid molecular imprinted polymers and aptamers for the detection of protein biomarkers
• Electrochemical detection of microRNAs (with femtomolar levels of detection)
• Lab-on-a-disk approaches using antibody fragments for PSA and HER2
• Si nanowires field-effect transistors
• Graphene oxide field-effect transistors
• Si nanowire-based memristors
Furthermore, sensors that can detect the levels of anti-cancer drugs in blood have also been developed. These will enable a personalised therapeutic approach to PCa.
Levels of sensitivity for the above approaches have been achieved that enable the detection of markers within the clinically relevant ranges. Most devices have also been shown to operate in blood serum.
The selection of the devices to be taken forward towards clinical validation depends on the markers that need to be tested and the type of sample to be used (e.g. blood, urine, biopsy sample)
The scientific results arising from PROSENSE were very significant. This resulted in 55 papers published in international peer-reviewed journals, 7 conference proceedings paper and 3 book chapters. A number of further papers have already been submitted for publication or are in the final stages of preparation. Furthermore over 50 presentations have been given at national and international conferences.
Many of the publications arose from new collaborations between the partners, made possible through the Fellows' secondments within PROSENSE.
The Fellows within PROSENSE received multidisciplinary training in a range of disciplines, methods and techniques: e.g. antibody production, protein glycosylation principles and detection, microfluidics, electrochemistry, nanofabrication, theranostics, biosensor construction. In addition, generic skills training was offered in a wide range of topics (e.g. career development, grant applications, presentation skills, patents, etc).
The interaction between the Fellows was extremely intensive and benefitted them and their research groups. A large number of collaborations were established through these interactions, including several initially unplanned collaborations.
Several of the ESR Fellows have finished theirs PhDs or submitted their theses for examination, while others were given extensions within their institutions in order to finalise their theses. All of the ER Fellows are on employment in industry or academia.
Further details on the published PROSENSE results are available in www.prosense-itn.eu
Hence, we need to set out to identify early predictive markers of prostate cancer that can be integrated with reliable and robust sensing platforms, which may be useful for early diagnosis as well as to predict the clinical outcome and treatment response.
The Marie Curie Initial Training Network PROSENSE (2012-2016) aimed at meeting the major challenges in the development of diagnostic tools for prostate cancer by training a new generation of young scientists in multidisciplinary techniques and methods.
PROSENSE was a coordinated research training network involving academic, industrial and clinical partners. PROSENSE was a unique programme bringing together training across disciplines and across sectors, complemented by researcher career development tools.
PROSENSE was a coordinated research training network involving university groups, R&D sections of small and medium enterprises, research institutes, hospitals and the R&D section of a large enterprise from the biomedical field.
The scientific aspects of PROSENSE were centred around the themes of:
• Development and study of biomarkers
• Detection techniques development
• Probe immobilisation and characterisation
• System integration and validation
A full programme of cross-disciplinary and cross-sectoral secondments, training and events enabled PROSENSE to promote interaction, knowledge exchange and collaboration in the multidisciplinary field of biosensor design with the aim of developing improved devices for prostate cancer diagnosis, prognosis and treatments.
It improved sensitivity, selectivity, robustness and speed of biosensing technologies for the simultaneous screening of biomarkers; developed lab-on-a-chip devices requiring minute amounts of clinical samples and increase likelihood of viable fit-for-purpose prostate cancer biosensing products.
Work on the different scientific work packages has been progressed with a number of significant results. PSA was used as a test biomarker for the development of the majority of the sensors, since this marker is currently the gold standard in PCa diagnosis (even though it is not a very reliable marker). However, most of the techniques can be adapted for other markers present in blood or urine.
A few of the sensors developed are singleplex, i.e. they measure only one marker at a time. An example is the inexpensive lateral flow devices for PSA and for PSA glycosylation as well as the optical chemiluminesce sensors in a microfluidic device and the magnetic bead-based electrochemical sensors.
The majority of the sensors however can be explored in a multiplex system, i.e. platforms that can be expanded to measure a panel of biomarkers at the same time. These include:
• DNA aptamer based electrochemical sensors for PSA, AMACR, HER2, PSA glycosylation
• Use of field-effect transistors with aptamers or hybrid molecular imprinted polymers and aptamers for the detection of protein biomarkers
• Electrochemical detection of microRNAs (with femtomolar levels of detection)
• Lab-on-a-disk approaches using antibody fragments for PSA and HER2
• Si nanowires field-effect transistors
• Graphene oxide field-effect transistors
• Si nanowire-based memristors
Furthermore, sensors that can detect the levels of anti-cancer drugs in blood have also been developed. These will enable a personalised therapeutic approach to PCa.
Levels of sensitivity for the above approaches have been achieved that enable the detection of markers within the clinically relevant ranges. Most devices have also been shown to operate in blood serum.
The selection of the devices to be taken forward towards clinical validation depends on the markers that need to be tested and the type of sample to be used (e.g. blood, urine, biopsy sample)
The scientific results arising from PROSENSE were very significant. This resulted in 55 papers published in international peer-reviewed journals, 7 conference proceedings paper and 3 book chapters. A number of further papers have already been submitted for publication or are in the final stages of preparation. Furthermore over 50 presentations have been given at national and international conferences.
Many of the publications arose from new collaborations between the partners, made possible through the Fellows' secondments within PROSENSE.
The Fellows within PROSENSE received multidisciplinary training in a range of disciplines, methods and techniques: e.g. antibody production, protein glycosylation principles and detection, microfluidics, electrochemistry, nanofabrication, theranostics, biosensor construction. In addition, generic skills training was offered in a wide range of topics (e.g. career development, grant applications, presentation skills, patents, etc).
The interaction between the Fellows was extremely intensive and benefitted them and their research groups. A large number of collaborations were established through these interactions, including several initially unplanned collaborations.
Several of the ESR Fellows have finished theirs PhDs or submitted their theses for examination, while others were given extensions within their institutions in order to finalise their theses. All of the ER Fellows are on employment in industry or academia.
Further details on the published PROSENSE results are available in www.prosense-itn.eu