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Updated: May 5, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Towards Precision Medicine in Metastatic Renal Cell Carcinoma: The Role of Emerging Biomarkers
Rugile Pikturniene1,2, Alvydas Cesas2, Sonata Jarmalaite1
1Life Sciences Center, Institute of Biosciences, Vilnius University, 01513 Vilnius, Lithuania.
Abstract:
RCC remains a therapeutically challenging malignancy, particularly in its metastatic stage, in which treatment resistance and limited response durability persist despite recent advances in immunotherapy and targeted therapies. Although immune checkpoint inhibitors (ICIs) have significantly improved outcomes for a subset of patients, reliable prognostic and predictive biomarkers to guide therapy selection are still lacking. Current clinical models, such as the International Metastatic RCC Database Consortium (IMDC) risk score, offer only limited insight into the molecular and immunologic complexity of RCC. Emerging molecular biomarkers implicated in resistance mechanisms reflect the underlying heterogeneity of RCC and may inform future therapeutic strategies. Kidney Injury Molecule-1 (KIM-1), a transmembrane protein that is up-regulated in RCC and detectable in circulation, has demonstrated potential as a non-invasive biomarker for diagnosis, prognosis, and treatment monitoring. Liquid-biopsy approaches, including the analysis of circulating tumour DNA (ctDNA), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), are also gaining traction due to their minimally invasive nature and potential for real-time disease monitoring. This review aims to provide a structured overview of emerging biomarkers in metastatic RCC, critically evaluate their current clinical applicability, and propose a biologically informed framework for their integration into clinical decision-making. In addition, we propose a conceptual IMDC-Plus framework that integrates clinical, biological, and early dynamic markers to improve risk stratification in the era of immunotherapy (IO).
Insights
Metastatic renal cell carcinoma (RCC) presents treatment challenges. This review explores emerging biomarkers, like Kidney Injury Molecule-1 (KIM-1) and liquid biopsy markers, to improve risk stratification and guide immunotherapy (IO) selection.
Area of Science:
- Oncology
- Biomarker Discovery
- Translational Medicine
Background:
- Metastatic renal cell carcinoma (RCC) remains difficult to treat, with limited response durability to current immunotherapies and targeted therapies.
- Existing prognostic models, such as the International Metastatic RCC Database Consortium (IMDC) risk score, do not fully capture RCC's molecular and immunologic complexity.
- There is a critical need for reliable biomarkers to guide therapy selection and improve outcomes in metastatic RCC.
Purpose of the Study:
- To provide a structured overview of emerging biomarkers in metastatic RCC.
- To critically evaluate the clinical applicability of these novel biomarkers.
- To propose a framework for integrating biomarkers into clinical decision-making for improved risk stratification.
Main Methods:
- Literature review of emerging biomarkers in metastatic RCC.
- Analysis of biomarkers implicated in resistance mechanisms and heterogeneity.
- Discussion of liquid biopsy approaches (ctDNA, miRNAs, lncRNAs) and Kidney Injury Molecule-1 (KIM-1).
Main Results:
- Kidney Injury Molecule-1 (KIM-1) shows potential as a non-invasive biomarker for diagnosis, prognosis, and monitoring.
- Liquid biopsy markers (ctDNA, miRNAs, lncRNAs) offer minimally invasive, real-time disease monitoring capabilities.
- Emerging molecular biomarkers reflect RCC heterogeneity and can inform therapeutic strategies.
Conclusions:
- Novel biomarkers are essential for overcoming treatment resistance and improving outcomes in metastatic RCC.
- Integration of clinical, biological, and dynamic markers, forming a conceptual IMDC-Plus framework, can enhance risk stratification.
- Biomarker-guided therapy selection is crucial for optimizing immunotherapy (IO) effectiveness in metastatic RCC.
