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Urinary microbiota characterization of superficial bladder Cancer patients undergoing BCG immunotherapy

Grant number: 18/13996-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2018
Effective date (End): July 31, 2022
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Anamaria Aranha Camargo
Grantee:Vitor Heidrich
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Non-Muscle-Invasive Urothelial Carcinoma of the Bladder (NMIBC) accounts for 70-80% of all Bladder Cancer initial diagnoses. The standard treatment for NMIBC involves transurethral resection of the tumor, followed by intravesical immunotherapy with BCG. The clinical benefits of BCG therapy have been extensively documented. However, only 50% of the patients have long-lasting benefit, whereas the remaining patients present disease recurrence and progression following treatment. Furthermore, due to either local or systemic adverse events, between 5 and 20% of BCG-treated patients present intolerance to therapy during its distinct phases. Therefore, the identification of biomarkers for predicting clinical benefit and toxicity to BCG therapy is instrumental for a personalized management of Bladder Cancer patients. Recent studies highlighted the relevance of the gut microbiota composition for the efficacy of immune checkpoint blockade immunotherapy in Cancer patients and its direct association with treatment-related adverse events. These studies underlie the potential of the microbiota as a predictive biomarker of BGC response and toxicity. Interestingly, there is no data on the association between the urinary microbiota composition and BCG treatment outcome and toxicity in Bladder Cancer patients. In this study, we intend to characterize the urinary microbiota of superficial Bladder Cancer patients using metagenomics analysis of urinary samples collected before treatment and evaluate the relationship between microbiota composition, the occurrence of adverse events and BCG clinical benefit. This will allow the identification of predictive biomarkers of toxicity and clinical benefit to guide treatment of NMIBC patients. These studies may also provide a better understanding of the, not yet fully elucidated, mechanism of action of BCG therapy, enabling the development of new therapeutic approaches. (AU)