ReDrugBC · Novel therapeutic approaches, based on drug repurposing, for high risk non muscle invasive bladder cancer driven by patients’ proteomic signatures
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-06-01 → 2022-05-31
- EU contribution
- €162,806
- Participants
- 1
- Scheme
- MSCA-IF-EF-SE
Lines connect the coordinator with its partners.
Results in brief
Novel therapeutic approaches, based on drug repurposing, for high risk non muscle invasive bladder cancer driven by patients’ proteomic signatures
The main problem that ReDrugBC is attempting to tackle is the therapeutic challenges at earlier stages of bladder cancer (BC). Despite the recent progress in diagnosis and management, BC remains among the most prevalent cancers worldwide and one of the most costly malignancies to treat on a per-patient basis. For patients with Non-Muscle Invasive BC (NMIBC; accounting for 70% of new BC cases) the standard of care is transurethral resection of the bladder tumor followed by adjuvant intravesical treatment regimens. For Muscle Invasive BC (MIBC; represents the remaining 30% of the BC cases), cisplatin-based chemotherapy followed by radical cystectomy is the gold standard for treatment. Despite recent progress in the treatment of advanced BC through the application of immune checkpoint inhibitors, management especially of high risk NMIBC is clearly suboptimal and to a large extent empirical. Better management, especially at this relatively earlier disease phase, can be of significant added value via impeding disease progression to more advanced, lethal and costly phases. ReDrugBC project has both strong societal and economic impact. ReDrugBC Project introduces the concept of drug repurposing in BC, a concept not previously explored for this disease. Drug repurposing is a cost-effective strategy that targets the re-use of existing de-risked drugs for new therapeutic purposes by combining machine-learning computational methods with large-scale patients’ multi-omics data. The suggested pipeline in ReDrugBC could open new avenues towards effective BC treatment, especially at earlier stages of the disease that may accelerate clinical trials and open new avenues towards personalized therapy for BC. In order to best address the current needs for improved BC treatment options, ReDrugBC aims at the identification of novel drug candidates that have the potential of reversing BC aggressiveness using the molecular signatures of the patients. This objective is expected to be achieved through the following three specific tasks: 1) Drug identification (via drug repurposing) based on the tissue molecular profile (available proteomics integrated with information on the transcriptome level) of patients with BC. 2) Evaluation of the impact of candidate drugs in vitro in BC cell lines. 3) Characterization of the proteomic profile of cell lines for the presence of the drug response signature and the molecular impact of the administered compounds. Conclusions: ReDrugBC unveiled promising drug candidates that have the potential to reverse BC aggressiveness. The research and training activities boosted the IF fellow career in the industrial sector.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- MOSAIQUES DIAGNOSTICS GMBH · HannoverCoordinatorGermany
Links
Data: CORDIS, © European Union