Liquid biopsies have been heralded as a game changer in cancer management, with blood tests offering a minimally invasive, safe, and sensitive alternative or complimentary approach for tissue biopsies. With a predicted 21 million new cancer cases and 13 million cancer deaths per year by 2030, this prospect must urgently materialise in the clinic.
Blood represents a rich source of information through which solid cancers (and their subtypes) can be detected, identified and classified, and matched to a specific therapy. Currently, blood-based biopsy measurements focus on 4 main biomarker sources (further referred to as biosources) – tumour educated platelets (TEPs), circulating tumour DNA (ctDNA), circulating tumour cells (CTCs) and extracellular vesicles (EVs; exosomes, oncosomes). Despite the potential of individual techniques, each has its own disadvantages which should be considered before broad rollout in clinical practice. Implementation is hampered by challenges with isolation of nucleic acids, standardisation of analysis techniques, validation of biomarkers, proof of clinical utility and cost-effectiveness. It is our conviction that, while researchers in general focus on one or two biosources, without an integrative approach individual limitations will be difficult to overcome. In addition, researchers have limited knowledge on what it takes to bring such a technology to market and the field is so new that regulatory requirements for clearance are unclear. To date only a handful of liquid biopsy tests have received CE mark and/or FDA approval, preventing broader liquid biopsy implementation. Widespread deployment requires a unique toolbox, including medical know-how, molecular diagnostics expertise (from health economics to regulatory), and statistical/bioinformatical proficiency. We need creative next-generation researchers with an innovative mindset that know how to circumvent the obstacles on the liquid biopsy development and commercialisation path. Currently, there are no comprehensive training programmes to address this need. To move this promising technology out of its infancy, the research programme and educational curriculum of the European Liquid Biopsy Academy (ELBA) will cover the entire value chain of diagnostics development and integrate all required disciplines and sectors.
Scientific objectives: This large integrated project will cover the development and implementation of innovative diagnostics, including assay development, bioinformatics, clinical validation, standardisation and comparison of 4 blood-based biosources and technologies aimed at NSCLC. A fifth innovative ELBA component concerns the development of a breakthrough technology for analysis of the 4 biosources: functional assays. The project outputs will tell which blood test or combination of tests based on CTCs, ctDNA, EVs, or TEPs will be technically robust for large-scale validation. ELBA will pursue 5 scientific objectives:
1. To get comprehensive clinically relevant information out of individual standardised blood-based biosources and pinpoint diagnostic synergy by combination of biosources
2. To identify and validate biomarkers for detection of stage I-IV NSCLC in a case-controlled study for future liquid biopsy screening programmes
3. To identify and validate biomarkers for selection of NSCLC patients for treatment, including PD1-PDL1 immunotherapies, and targeted therapies aimed at the kinases EGFR, MET, ALK, PIK3CA, VEGFR, MTOR, and AKT, amongst others
4. To establish novel bio-informatics tools and protocols for the integrative analysis of multi-source liquid biopsy data of DNA
and RNA molecules, including data analysis and machine learning aspects
5. To develop blood-based assays to deliver scalable prototypes capable of obtaining regulatory approval
Training objectives: ELBA aims to deliver 15 ESRs with a helicopter-view across fields and disciplines, with in-depth knowledge of diagnostic applications of liquid biopsies. ESRs will draft a personal training and career development plan depending on his/her profile and training needs and wants. To that end, ELBA will pursue 5 training objectives:
1. To enable 15 ESRs to become front-runners in the field of liquid biopsies, focused on acquiring understanding of biomarker
identification/validation, molecular diagnostics, bioinformatics/biostatistics and beyond-the-state-of-the-art technologies.
2. To build a solid collaborative network aimed at future alliances that will function as a springboard for new talent, by allowing
strong international, interdisciplinary and intersectoral interactions between ESRs and project participants.
3. To stimulate an entrepreneurial mindset, by training the ESRs in applying transdisciplinary innovation management skills
and practices in medical technology, by offering BioBusiness workshops and secondments at industry participants.
4. To allow ESRs to reach their full potential and maximise employability, with a set of training courses aimed at strengthening transferable skills (e.g. leadership, interpersonal communication, team/network building, ability to work in multidisciplinary
teams, can-do mentality, thinking out-of-the-box).
5. To teach the ESRs how to perform research and development activities with the patient in mind.