Effects of Photobiomodulation Combined with Bacillus Calmette-Guérin on Cellular Energy Metabolism and Treatment of Non-Muscle Invasive Bladder Cancer

• Grant number: 24/09248-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Wagner José Fávaro
• Grantee: Wesley Chaves de Oliveira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The development and progression of cancer are characterized by a unique reprogramming of energy metabolism, essential to sustain the highly proliferative neoplastic cells. Investigating energy metabolism in neoplastic cells is crucial for understanding how these cells support their rapid growth and proliferation, particularly under adverse conditions of nutrient and oxygen availability. In the case of non-muscle invasive bladder cancer (NMIBC), this understanding is even more critical due to the profound metabolic anomalies that characterize this cancer type. Several altered metabolic pathways play a crucial role in bladder tumorigenesis, making them attractive targets for new therapies. The treatment of bladder cancer has evolved to include immunotherapies, alongside standard modalities such as surgery and chemotherapy. However, many high-risk NMIBC patients do not respond to Bacillus Calmette-Guérin (BCG), necessitating new therapeutic alternatives. In response to this need, our research group has developed Photobiomodulation (PBM) combined with BCG treatment, demonstrating significant relevance and therapeutic potential for positive outcomes in oncological treatment, especially for NMIBC. PBM is a treatment method comprising three non-toxic elements: a photosensitizer, molecular oxygen, and light at a specific wavelength, which together produce reactive oxygen species, particularly singlet oxygen as a cytotoxic agent. Considering a bladder-sparing approach, PBM can be used in NMIBC patients in conjunction with BCG, aiming to enhance the modulation of cellular energy metabolism. To date, no studies have investigated the concurrent treatment of PBM on cellular energy metabolism to improve BCG responses in NMIBC. Thus, the objectives of the present research project are to characterize and compare the histopathological and molecular effects of BCG immunotherapy, PBM, and their combination in the treatment of chemically induced NMIBC in rats, as well as to establish the possible mechanisms of action of these therapies, with an emphasis on cellular energy metabolism. Additionally, the project aims to evaluate the cellular bioenergetic index (IBEC) to establish a clinically relevant criterion with prognostic significance and the ability to predict treatment responses.