Plasma proteomics for biomarker discovery in Renal Cancer Patients undergoing immunotherapy

• Grant number: 25/01364-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 17, 2025
• End date: December 19, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Leandro Machado Colli
• Grantee: Virgínia Campos Silvestrini
• Supervisor: Amanda G Paulovich
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Fred Hutchinson Cancer Research Center (Fred Hutch), United States
• Associated to the scholarship: 22/14894-2 - PROTEOGENOMIC EVALUATION OF PATIENTS WITH KIDNEY CANCER TREATED WITH IMMUNOTHERAPY, BP.PD

Abstract

Renal cell carcinoma (RCC) accounts for 2-3% of all cancers worldwide and is among the top ten most diagnosed malignancies, with higher incidence rates observed in Western countries. Among the RCC subtypes, clear cell renal cell carcinoma (ccRCC) is the predominant histology, representing 85% of cases. Treatment typically involves targeted therapies against vascular endothelial growth factor (VEGF) and novel immunotherapeutic agents. Among these, immune checkpoint inhibitors (ICIs) have emerged as the first-line therapeutic option for ccRCC, demonstrating improved clinical outcomes. These agents include ipilimumab and nivolumab, monoclonal antibodies that target CTLA-4 and PD-1, respectively. However, despite their significant impact on renal cancer treatment, several challenges remain. It is estimated that 44% of cancer patients in the United States are eligible for ICI therapy, yet only 12% respond to treatment, with many developing resistance mechanisms that remain poorly understood. Furthermore, while some patients experience complete tumor regression, others exhibit hyper-progression. This underscores the urgent need to elucidate the mechanisms underlying resistance and identify novel molecular targets involved in the process. The CLARA is a clinical study that aims to address these challenges by recruiting 100 patients with metastatic renal cancer who are undergoing immunotherapy treatment. The objective is to identify somatic and germline mechanisms of response and resistance to treatment. As part of this study, we have already conducted a global proteomic analysis of 73 patients at various stages of immunotherapy. The next phase involves proteomic analysis of plasma samples from these patients at different time points during therapy. This approach will enable the identification of tumor-secreted proteins and prognostic markers.