The role of microenvironment in the aggressiveness and sunitinib-resistance of clear cell renal cell carcinoma

• Grant number: 24/04272-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 05, 2024
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Céline Marques Pinheiro
• Grantee: Patrik da Silva Vital
• Supervisor: Yasser Riaz Alhosseini
• Host Institution: Hospital do Câncer de Barretos. Barretos , SP, Brazil
• Institution abroad: Mcgill Genome Centre, Canada
• Associated to the scholarship: 22/09996-0 - The role of metabolism in the aggressiveness and sunitinib-resistance in Clear Cell Renal Cell Carcinoma, BP.DR

Abstract

Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for 75-85% of renal malignancies, being the most lethal subtype of urological cancers. Despite the presence of immunotherapy in clinical practice, sunitinib is frequently used for the treatment of ccRCC, and is even adopted by the Brazilian public health system (SUS) for metastatic cases. However, approximately 70% of patients develop resistance to this drug within one year. The biology of ccRCC is highly complex, influenced by a multitude of factors including metabolism, immunology, and genetics. This complexity underscores the essential role of holistic studies in discovering new treatments and biomarkers for this type of cancer. Unfortunately, such studies are scarce, particularly in the context of treatment resistance. Objective: The objective of this project is to evaluate the role of the tumor microenvironment in ccRCC in the context of resistance to sunitinib. Methods: A comprehensive multiomic analysis will be conducted to investigate the association between sunitinib response and microenvironmental alterations in ccRCC tumors. To achieve this, the present study will encompass spatial transcriptomic analysis of a cohort of 60 ccRCC patients who received sunitinib treatment, and validation using RNA-seq ccRCC datasets and patient-derived organoid (PDO) models. Conclusion: The intricate complexity of the ccRCC microenvironment warrants a comprehensive multiomic approach to elucidate potential biomarkers and therapeutic targets for effective treatment strategies. By unraveling the intricate interplay between alterations in ccRCC microenvironment and sunitinib response, this study aims to enhance our understanding of ccRCC biology and improve patient outcomes. (AU)