VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells

Area of Science:

• Oncology
• Metabolic Research
• Cancer Therapy

Background:

• Anti-VEGF therapy impacts tumor metabolism, reducing oxygen, glucose, and ATP.
• Tumor glycolytic phenotype influences response to anti-VEGF treatment.

Purpose of the Study:

• Investigate anti-VEGF therapy effects on tumors with varying glycolytic phenotypes.
• Understand optimal metabolic modulation strategies for anti-VEGF therapy.
• Explore the role of tumor cell-autonomous metabolic traits in treatment resistance.

Main Methods:

• Utilized multiple experimental tumor xenograft models with differing glycolytic phenotypes.
• Administered prolonged anti-VEGF treatments.
• Employed Positron Emission Tomography (PET) imaging.
• Performed serial transplantation studies in mice.

Main Results:

• Prolonged anti-VEGF treatment induced vascular regression and necrosis.
• Highly glycolytic tumors developed resistance faster than poorly glycolytic tumors.
• PET imaging revealed increased hypoxic and proliferative regions post-treatment.
• A stable, cell-autonomous selection for highly glycolytic cells was observed, correlating with increased aggressiveness and resistance.

Conclusions:

• The highly glycolytic phenotype is a cell-autonomous trait conferring resistance to VEGF blockade.
• Antiangiogenic therapy can select for specific tumor metabolic traits, influencing evolutionary dynamics.
• Understanding and modulating tumor metabolism is crucial for optimizing anti-VEGF therapy efficacy.