Scholarship 24/04272-0 - Biomarcadores tumorais, Resistência a medicamentos - BV FAPESP
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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 until: September 05, 2024
End date until: 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. Fundação Pio XII (FP). 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.

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