Joint Call (JTC 2016)

The third call of TRANSCAN-2 (JTC 2016) focuses on: “Minimally and non-invasive methods for early detection and/or progression of cancer”.Minimally invasive methods refer to techniques that have limited physical damage, burden and pain associated with the detection method, resulting in less anticipated stress, a higher screening/clinical care uptake, and more efficient and cost-effective screening and care.The studied methods should be sensitive for early detection of cancer, its staging and prediction of progression.

Examples are: individual or combination of molecular, immunochemical, proteomic or genetic markers in body fluids and blood or cell samples, as well as macroscopic, microscopic and molecular imaging techniques (e.g. improved ultrasound technology, molecular imaging with contrast agents, fluorescence imaging, radiolabelling).This call excludes invasive methods, such as image-guided biopsy or surgery.In the context of translational cancer research, this topic will comprise three specific aims.

Proposals will have to cover at least one of the specific areas listed under each undermentioned aim.

Aim 1: Risk stratification to distinguish groups by susceptibility for development or progression of cancer based on molecular biomarkers and established cancer risk factors, such as age, medical history, anthropometrics (e.g., body mass index, waist circumference), and lifestyle related determinants (e.g., diet, physical exercise, environmental exposure and medication).- Risk stratification for cancer development (susceptibility to develop cancer) using minimally invasive methods (imaging, biomarkers assessment in body fluids) to identify high risk groups of individuals who will benefit most from a more intensive and/or invasive screening.- Risk stratification for cancer progression (biomarker(s) or clinical characteristic(s) with a prognostic value, i.e. that provides information on the likely outcome of the cancer in (untreated) individuals).

Detection of tumour promoting subpopulations, those with enhanced ability to drive tumour progression.

Aim 2: Validation of multiparametric methods, using the combination of promising[1] biomarkers (genomic, proteomic, metabolomic and imaging markers) to improve our capability for early detection or progression of cancer.Different tumour markers show different sensitivity towards different types of tumours.

Combining multiple markers significantly increases the ratios of positive cancer diagnosis.

Even though the increase in sensitivity when combining markers and tools might be accompanied by a decrease in specificity, tumour markers combinations may still play an important role in early tumour detection as well as in prediction of cancer progression.As high throughput genomic assays become more accessible, working with largescale data sets requires user-friendly and powerful tools and techniques to help researchers manage, analyse and integrate big data from genomics.

The development and implementation of adequate bioinformatics techniques are of essential importance.

Biomarkers that are suitable for automated measurement are promising tools.- Molecular tumour markers: increase sensitivity of detecting genetic, epigenetic or proteomic markers, including circulating tumour cells (CTC techniques), exosomes, tumour DNA, circulating free DNA in plasma and other fluids, micro RNA and integration with metabolomic assays.- Imaging markers: such as low radiation CT scans or intravenously delivered fluorescent peptide probes.- Bioinformatics techniques: techniques for mining complex genomic/biomarkers data.[1] Biomarkers that already have shown to have predictive value, but need to be validated in an independent heterogeneous target population.

Aim 3: Improve clinical evidence of the minimally invasive methods.Important criteria to evaluate a biomarker are described in the ACCE model.

It is important to acknowledge these criteria when describing the outcome measures and future directions of the project plan.- Analytical validity, clinical validity, and clinical utility: evaluation (or describe the planning) of the impact of minimally invasive methods on patient outcome (less invasive detection, increased life expectancy, or reduced morbidity) and properties such as sensitivity and specificity.Ethical, legal, and social implications (could also be considered): evaluation of implication and implementation aspects, e.g. acceptance of personalised screening based on risk stratification.