Precision Bladder-Preservation: Integrating Multi-Omics for Personalized Bladder Cancer Therapy

To enhance the effectiveness of bladder-preservation therapy, by integrating multi-omics data to identify key determinants of RT efficacy, enabling the development of personalized therapeutic strategies: To achieve this, our aims are: 

1. Develop a predictive model by integrating gut microbiome, metabolomic, transcriptomic, and genome and immune profiling data to identify biomarkers of response to bladder-preservation therapy. 
2. Investigate how Tumor Microenvironment influence RT response, providing a rationale for interventional strategies.
3. Validate findings in preclinical models and patient-derived xenografts (PDX) to explore novel therapeutic approaches and interventional strategies 

Bladder cancer is the most common cancer of the urinary tract and a major health concern. It has a high chance of coming back after treatment, making it one of the most expensive and difficult cancers to manage. The standard treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which involves removing the bladder. While this can be effective, it comes with serious physical and emotional challenges, affecting a patient’s quality of life. Unfortunately, nearly half of MIBC patients are not healthy enough for surgery, leaving them with limited treatment options. 

Radiation therapy (RT) is an alternative that allows patients to keep their bladder, maintaining a better quality of life. However, it does not always work—about 30% of patients still need surgery later, and half may develop cancer spread (metastasis). Since we do not fully understand why some patients respond well to RT while others do not, there is an urgent need for better tools to predict treatment success and guide personalized care. 

Our research aims to improve bladder-preservation therapy by using advanced scientific techniques to understand why some tumors respond better to treatment than others. We will achieve this by analyzing multiple layers of patient data (multi-omics), including the gut microbiome, metabolism, tumor and immune system interactions, and genetic and molecular profiles. The bacteria in our gut influence how our immune system fights cancer, and certain gut bacteria may enhance responses to radiation therapy (RT) and immunotherapy. Metabolic molecules, produced by food and gut bacteria, can either strengthen the immune system’s ability to attack cancer or contribute to its suppression. Additionally, studying tumor cells and their surrounding immune environment will help us understand what makes certain tumors more resistant or sensitive to treatment. Genetic and molecular profiling will provide insights into specific gene activity and mutations that impact RT outcomes.  

To integrate this multi-omics data, we will combine information from electronic medical records, imaging archives, biobank repositories, and histological datasets. Machine-learning algorithms will be applied for feature selection and predictive modeling of RT response. This approach will allow us to uncover critical biomarkers and biological pathways that influence treatment success, paving the way for precision medicine in bladder cancer care. 

The ability to predict treatment response could transform bladder cancer management by focusing to personalized therapy’s approaches tailored to a patient’s unique biology. More accurate treatment plans would help reduce unnecessary therapies and side effects while increasing the success rate of bladder-preserving treatments, allowing more patients to keep their bladder. By improving survival rates and preventing cancer spread through better treatment strategies, this research could also identify new therapeutic targets that pave the way for future innovations in bladder cancer therapy. 

MOH value:  Implementing multi-omics predictive algorithms into clinical practice has the potential to revolutionize bladder cancer care, leading to more effective, personalized treatment decisions. This precision-medicine approach will not only improve patient outcomes and quality of life but also foster novel discoveries in bladder cancer research, positioning MUHC as a leader in precision oncology and bladder-preservation therapy