TheranOMICS Project aims at the recruitment of a highly-qualified research Associate to support the Innovation Business Idea of Mosaiques diagnostics GmbH (MOS). The Associate is expected to have expertise in statistics, computer science and biology. The objective is the integration of high resolution bladder cancer (BC) –omics datasets that are available at MOS to establish molecular profiles which can predict disease outcome and treatment response. The tasks include application of state-of-the-art bioinformatics tools in the development of two predictive tools that together will be offered as a companion test to assist patient stratification and predict response in BC drug development. The first tool will be based on molecular features associated with the clinical status and will enable the stratification of BC patients to those with the higher probability to progress. The second tool will be built on molecules/biomarkers associated with drug response and will enable to prediction of success of chemotherapy, as a test case study. MOS Business Innovation Idea is the development of the above predictive tools, to be served as a "business-to-business" product for pharmaceutical companies developing Bladder Cancer (BC) drugs. The expected outcome is the improved stratification of BC patients and the increased efficacy of new therapeutic agents. The benefit for the customers (Pharmaceutical Industry) is the reduction of the number of investigated subjects, time requirement and cost of clinical trials. The benefit for MOS enterprise is the opening of new marketing possibilities and the positioning in the Market of Pharmaceutical Industry. As a secondary aim, we target implementation of the tools for BC Patient management, aiming at improved, personalized intervention to prolong patients’ lives and increase their quality of life. Thus, TheranOMICS aims beyond the one-year period of INNOSUP support and provides perspectives for the Associate for a long-term employment.

BioMedBC Proposal is focused on improving the patient management of Bladder Cancer (BC). BC presents with the highest recurrence rate and the highest associated costs of all cancers. Due to the intrinsic heterogeneity, the investigated drugs in clinical trials, cannot be easily introduced in the clinical practice. Molecular profiles/ biomarkers (BM) with predictive potential are required to enable patient stratification. The BioMedBC proposal aims at the application of systems biology and cross-omics data integration methodologies to achieve: a) the molecular characterization of BC and b) develop signatures to predict the clinical outcome. To achieve these goals, integration of: i) high resolution proteomics datasets (planned to be acquired within BioMedBC), ii) existing datasets that were obtained in previous EU collaborative projects and iii) publicly available transcriptomics data, will be conducted, focusing on the molecular characterization of BC. Emphasis is given on the investigation of disease prognosis. For this purpose, clinical and follow-up data, available from ongoing prospective studies (n=1758), will be utilized for correlation analysis of the molecular profiles/ biomarkers with disease outcome (recurrence, progression and survival). The prognostic value will be confirmed in newly collected samples with emphasis placed on urinary protein/ peptide profiles, as non-invasive urinary markers is of significant added value. The innovation is held on the prognostic BM that can be further used to stratify patients to those that could be benefited by a potential intervention and guide personalized therapy to improve BC patient management. In parallel, BioMedBC aims at expanding upon the current training of the ER, Dr. Maria Frantzi, on transferability of the basic research results to clinically useful products and create strong career prospects for her desired development as an owner of a future SME.

The BioGuidePCa project is designed to validate previously reported biomarkers for prostate cancer (PCa) management during surveillance of early and advanced PCa. With availability of PSA-screening an increase of insignificant PCa has been observed leading to over-diagnosis and overtreatment. Consequently active surveillance (AS) is an alternative to immediate therapy. AS is expectant management with curative intervention only for those patients with local tumor progression. Neuhaus et. al reported a peptide panel, derived from seminal plasma for the estimation of PCa aggressiveness. A main objective of the project is the validation of these biomarkers in regards of its use in AS. On the other hand, advanced metastasized PCa is still a deadly disease. The majority of patients initially responding to therapy progress after a median duration of 30 months. Therapy of castrate resistant prostate cancer (CRPC) relies on hormone therapy and cytotoxic chemotherapy. Recent developments have resulted in novel substances for treatment. However the optimal sequence of the drugs has not been determined. Thus there is a clear clinical need for the development of new approaches for early detection of metastatic disease to guide initiation of alternative therapy. We have recently identified urine based biomarkers, specific for cancer progression. The second main objective of this project is to validate these peptides for their use in assessment of risk of progression and development of metastatic disease. Both biomarker panels will be developed into a non-invasive urine tests for the routine monitoring of CRPC and PCa progression. The study uniquely integrates leading PCa clinical experts with experts on proteome analysis and in an implementation-oriented workflow. The proposed study will provide strong evidence for utility of the new BMs and will set the foundation for diagnostic devices to guide early patient management and personalized therapeutic intervention in PCa and CRPC.

Bladder Cancer (BC) is the costlier cancer type to manage, characterized by high recurrence and progression rates. Despite recent advancements, current BC therapeutic strategies remain suboptimal, mostly due to the disease molecular heterogeneity. Profiling at the transcriptomics and, very recently, proteomics levels, revealed the existence of a cross-omics conserved molecular signature marking progression from low to high risk non muscle invasive (NMIBC) and eventually muscle invasive disease. ReDrugBC targets to identify drugs, via drug repurposing, able to revert the aggressive molecular signature for NMIBC, hence tackling the disease at an earlier stage and on a more holistic manner. To address this state-of-the-art concept, ReDrugBC is divided into three highly interrelated strategic points: 1) drug identification (among existing compounds) for NMIBC based on the existent tissue molecular profiles analyzed in a multi-layer and multi-omics manner using specialized bioinformatics-drug prediction tools, 2) definition of impact of selected drugs on the functional properties of BC cell lines in vitro and 3) characterization and understanding of the drug impact on a molecular level, via the application of high-throughput proteomics analysis. This research program will be carried out in a research intensive SME-leader in clinical proteomics and multi-dimensional analysis, by a very active and promising young researcher originating from academia, in a multidisciplinary, implementation-oriented manner. Outreach activities include among others links to pharmaceutical companies and regulators to accelerate progress towards (pre-) clinical trials post-ReDrugBC. Collectively, the proposed approach in ReDrugBC paves the way for better treatment of NMIBC via drug selection based on the patient molecular signatures, while offering unique inter-sectorial training on translational research to a highly motivated young female researcher.

The PCaProTreat Project targets on improving the Prostate Cancer (PCa) management and focuses on the identification of novel therapeutic targets for patients with an advanced disease stage. It has been demonstrated that the current medical practice has led to frequent over-treatment of patients exhibiting slow growing PCa (unlikely to progress in the absence of treatment), while for metastatic castration resistant patients that immediate treatment is required, no effective strategies are available. Therefore, new therapeutic options are required for advanced PCa. To address this clinical demand, PCaProTreat is focused on the comprehensive characterisation of the molecular background of PCa progression, based on which molecularly-driven therapeutic targets can be defined. Towards that end, PCaProTreat includes: a) multi-layer analysis (different types of specimens: tissue, urine, seminal plasma) and multi-omics profiling (proteomics, peptidomics, transcriptomics), supplemented with literature-mined data, b) establishment of the PCa knowledge database, c) data integration into Systems Biology workflow to identify key-regulatory elements responsible for disease progression (best suited drug targets) and d) validation of the selected targets using immunohistochemistry. This multi-dimensional approach represents a substantial advancement over the standards currently applied in drug discovery process, allowing to overcome the challenges associated with tumour heterogeneity and thus reveal optimal drug targets. In parallel to the research activities, a multi-disciplinary and multi-sectorial training program will be implemented to increase the competitiveness of the ER within the research community, to become a recognised researcher. Activities will be carried out in the industrial sector, with Mosaiques Diagnostics a leader in clinical proteomics and Systems Medicine, being a Host institution.