- A study led by researchers from IIBM and published in the journal European Urology identifies kidney tumors that could benefit from the combination therapy bevacizumab-erlotinib based on their molecular profile
The work, coordinated by Cristina Rodríguez-Antona from the Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), CSIC-UAM, and carried out in collaboration with the National Cancer Research Centre (CNIO), analyzes how the bevacizumab-erlotinib combination may benefit patients with metastatic renal tumors through the study of hypoxia response pathways and angiogenesis.
Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is an aggressive and rare type of kidney cancer that often goes undetected, as it can be mistaken for other renal tumors with papillary morphology. However, recent studies have shown that these tumors respond particularly well to the combination of bevacizumab and erlotinib, with response rates of up to 80%.
To investigate how many patients might be receiving incorrect diagnoses, the team analyzed renal tumors initially classified as papillary carcinomas or unclassified renal tumors. The study revealed that 16% of metastatic cases harbored mutations in the FH gene, compared to less than 1% in localized tumors, further underscoring the especially aggressive nature of this tumor subtype.
The researchers also investigated why some tumors respond better to bevacizumab-erlotinib therapy. Through transcriptomic analyses, they observed that FH-RCC tumors display high activation of angiogenesis and EGFR receptor pathways, two biological mechanisms directly linked to the action of these drugs.
Building on these findings, the team also identified a subset of papillary renal carcinomas with molecular activation patterns similar to FH-RCC cases, which could likewise benefit from this treatment. According to the authors, approximately 18% of papillary renal carcinomas may belong to this group potentially sensitive to the therapy.
The study recommends incorporating FH-deficiency testing — through genetic analysis or immunohistochemical techniques — in metastatic renal tumors with papillary morphology, given its diagnostic and therapeutic implications.
The authors highlight that these findings extend the use of the bevacizumab-erlotinib combination beyond FH-RCC, and could even open the door to other tumors with metabolic alterations related to the Krebs cycle.
The work, whose first author is Javier de Nicolás-Hernández (IIBM), involved researchers from IIBM, CNIO, and CIBERER. This study is part of a research line of the Pharmacogenomics and Tumor Biomarkers Group at IIBM, focused on precision medicine and molecular biomarkers in renal cancer. Taken together, these results reinforce the potential of personalized medicine to improve treatment selection and open new therapeutic perspectives for patients with kidney cancer.