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Updated: Apr 21, 2026
Preparation Of Neovascular Tissues from Human Glioma Tissues for Quantitative Proteomics Analysis of Tumor Angiogenesis
Published on: March 20, 2026
Neoadjuvant antiangiogenic therapy reveals contrasts in primary and metastatic tumor efficacy
John M L Ebos1, Michalis Mastri2, Christina R Lee3
1Genitourinary Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA John.Ebos@roswellpark.org.
Abstract:
Thousands of cancer patients are currently in clinical trials evaluating antiangiogenic therapy in the neoadjuvant setting, which is the treatment of localized primary tumors prior to surgical intervention. The rationale is that shrinking a tumor will improve surgical outcomes and minimize growth of occult micrometastatic disease-thus delaying post-surgical recurrence and improving survival. But approved VEGF pathway inhibitors have not been tested in clinically relevant neoadjuvant models that compare pre- and post-surgical treatment effects. Using mouse models of breast, kidney, and melanoma metastasis, we demonstrate that primary tumor responses to neoadjuvant VEGFR TKI treatment do not consistently correlate with improved post-surgical survival, with survival worsened in certain settings. Similar negative effects did not extend to protein-based VEGF pathway inhibitors and could be reversed with altered dose, surgical timing, and treatment duration, or when VEGFR TKIs are combined with metronomic 'anti-metastatic' chemotherapy regimens. These studies represent the first attempt to recapitulate the complex clinical parameters of neoadjuvant therapy in mice and identify a novel tool to compare systemic antiangiogenic treatment effects on localized and disseminated disease.
Insights
Neoadjuvant antiangiogenic therapy, including VEGFR TKIs, does not consistently improve survival in preclinical cancer models. Combining VEGFR TKIs with chemotherapy or altering treatment timing can mitigate negative effects on survival.
Area of Science:
- Oncology
- Cancer Research
- Translational Medicine
Background:
- Antiangiogenic therapy is being evaluated in neoadjuvant clinical trials for localized primary tumors before surgery.
- The goal is to improve surgical outcomes and reduce cancer recurrence by shrinking tumors.
- Clinical models are lacking to compare pre- and post-surgical antiangiogenic treatment effects.
Purpose of the Study:
- To evaluate the efficacy of neoadjuvant antiangiogenic therapy in preclinical models.
- To compare the effects of VEGFR TKIs and protein-based VEGF inhibitors.
- To identify strategies for optimizing neoadjuvant antiangiogenic treatment.
Main Methods:
- Utilized mouse models of breast, kidney, and melanoma metastasis.
- Administered neoadjuvant VEGFR TKI treatment and protein-based VEGF inhibitors.
- Assessed primary tumor response, post-surgical survival, and treatment modifications.
Main Results:
- Neoadjuvant VEGFR TKI treatment did not consistently correlate with improved post-surgical survival, and sometimes worsened it.
- Negative effects of VEGFR TKIs were not observed with protein-based VEGF inhibitors.
- Adverse survival outcomes were reversible with dose/timing adjustments or combination chemotherapy.
Conclusions:
- Neoadjuvant VEGFR TKI efficacy is context-dependent and may not improve survival.
- Protein-based VEGF inhibitors may offer a safer alternative in certain settings.
- Optimized dosing, timing, and combination regimens are crucial for neoadjuvant antiangiogenic therapy.
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