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Updated: Dec 9, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Prospective Translational Study Investigating Molecular PrEdictors of Resistance to First-Line PazopanIb in
Pierangela Sepe1, Antonia Martinetti1, Alessia Mennitto1
1Department of Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan.
Objectives:
Despite the initial clinical benefit, resistance to antiangiogenic therapies develops through the activation of alternative pathways. We measured plasma levels of circulating angiogenic factors to explore their predictive role in metastatic renal cell carcinoma (mRCC) patients treated with pazopanib.
Materials And Methods:
mRCC patients receiving first-line pazopanib were prospectively enrolled. The levels of circulating interleuchine (IL)-6, IL-8, stromal derived factor-1, vascular endothelial growth factor-A, hepatocyte growth factor (HGF), osteopontin, and E-selectin were quantified at baseline and every 4 weeks until disease progression (PD). Patients were dichotomized into "low" and "high" subgroups by a cutoff point defined by the respective median circulating angiogenic factor (CAF) value at baseline. Then, association with the objective response was determined. Changes in CAF levels between baseline and PD were also compared.
Results:
Among 25 patients included in the final data set, 6 patients were still on treatment. As best response, 12 patients presented a partial response (48%), 9 showed stable disease, and 4 showed PD. The median follow-up was 31.9 months. The median progression-free survival was 14.8 months. Low baseline levels of IL-6, IL-8, HGF, and osteopontin were found to be significantly associated with objective response. In addition, patients with low baseline levels of HGF showed longer progression-free survival and overall survival, whereas patients with low baseline levels of IL-8 showed longer overall survival. Among patients experiencing PD, the median plasma levels of stromal derived factor-1 and vascular endothelial growth factor-A were significantly higher compared with the baseline (P=0.01; P=0.011). Conversely, the median levels of E-selectin were significantly lower compared with the baseline (P=0.017).
Conclusion:
Changes in levels of selected CAFs were associated with response/resistance to pazopanib in mRCC patients.
Insights
Low baseline levels of certain circulating angiogenic factors predict response to pazopanib in metastatic renal cell carcinoma (mRCC). Changes in these factors indicate treatment resistance or progression.
Area of Science:
- Oncology
- Translational Research
- Biomarker Discovery
Background:
- Resistance to antiangiogenic therapies like pazopanib in metastatic renal cell carcinoma (mRCC) is a significant clinical challenge.
- Activation of alternative signaling pathways contributes to treatment failure.
Purpose of the Study:
- To investigate the predictive role of plasma circulating angiogenic factors (CAFs) in mRCC patients treated with pazopanib.
- To explore the association between baseline CAF levels and treatment response, as well as changes in CAF levels with disease progression.
Main Methods:
- Prospective enrollment of mRCC patients receiving first-line pazopanib.
- Quantification of plasma levels of IL-6, IL-8, SDF-1, VEGF-A, HGF, osteopontin, and E-selectin at baseline and during treatment.
- Dichotomization of patients into "low" and "high" CAF subgroups based on median baseline values.
Main Results:
- Low baseline levels of IL-6, IL-8, HGF, and osteopontin were significantly associated with objective response.
- Low baseline HGF correlated with longer progression-free and overall survival; low baseline IL-8 correlated with longer overall survival.
- Plasma levels of SDF-1 and VEGF-A increased, while E-selectin decreased at disease progression.
Conclusions:
- Changes in circulating angiogenic factor levels are associated with response and resistance to pazopanib in mRCC.
- Specific baseline CAFs may serve as predictive biomarkers for pazopanib efficacy in mRCC.
