BioMedBC · Molecular profiling of Bladder Cancer to support personalized medicine

Molecular profiling of Bladder Cancer to support personalized medicine

Clinical Problem/ Disease burden Bladder Cancer (BC) is the 4th most common cancer type in men and the 11th in women. It is characterized by the highest recurrence rate and is the costliest cancer type to manage. The majority of BC (~70%) are classified as Non Muscle Invasive (stages Ta,T1, Tis) and are treated by transurethral resection and BCG intravesical immunotherapy; whereas ~30% are Muscle Invasive (stages T2-4) and treated by radical cystectomy, (neo)adjuvant chemotherapy or (chemo)radiotherapy. Apart from cisplatin-based chemotherapy and cystectomy, recently introduced immunotherapy that targets PD-L1 molecule is recommended. Still the majority of BC patients do not respond to the current treatment. Clinical Challenges – Societal Impact Unraveling the molecular background of BC is important for the establishment of earlier therapeutic interventions. Moreover, accurate biomarkers (BM) for patient stratification are needed to guide intervention. BioMedBC Project focused on improving our understanding of BC at the molecular level and in deciphering molecular key elements implicated in disease outcome, in order to address the challenge of stratifying BC patients for their risk of progression and investigate novel drug targets based on the molecular pathology. This has a double impact, as patients can benefit from an earlier intervention, but also in drug development as patient stratification to those more likely to develop progressive disease or respond to therapy, is beneficial for selecting the most appropriate treatment. BioMedBC overall objectives BioMedBC focused on the identification of prognostic biomarkers based on molecular profiles for patient stratification and in order to assist appropriate treatment selection towards BC personalized medicine. This aim was formulated according to the following objectives: 1. The molecular characterization of BC, through cross-omics correlation of tissue and urinary proteomics datasets combined with publicly available transcriptomics data, 2. The delivery of predictive algorithms/ biomarkers, associated with disease outcome (prognostic value) and 3.The integration of data via bioinformatics tools to reveal molecular pathways and potential drug targets. Conclusions of the action BioMedBC project was completed according to the proposed plan in Annex I, without major deviations. The main achievements within the Project were: 1. The successful integration of the MSCA-IF Fellow 2. The close interaction between the MSCA-IF Fellow and the Supervisor, including a full training of the MSCA-IF Fellow 3. The development of prognostic biomarkers to stratify patients for the disease progression, focusing on urine as a desired context of use 4. The characterisation of the molecular pathology of BC and introduction of molecularly driven drug targets Altogether, BioMedBC Project resulted in the development of two sets of predictive biomarkers for patients’ stratification and response to treatment. Moreover, potential therapeutic approaches were introduced through Connectivity Map Analysis (CMap). The results were disseminated through several publications in scientific journals and also presented by the MSCA-IF fellow in international conferences (among others the 68th Lindau Nobel Laurette Meeting and the Benelux Precision Medicine Forum). Furthermore, the MSCA-IF fellow was trained in supervising and project management through the interaction with fellows from other EU projects, while in the context of BioMedBC project, the MSCA fellow co-edited a Special Issue in Proteomics Clinical Application.

Data: CORDIS, © European Union