Adaptive resistance of tumor cells to anti-vascular endothelial growth factor therapy: A reversible phenomenon.

• Tumor cells constitute the direct targets of anti-VEGF therapy; • Tumor cells possess the capacity to independently develop resistance to VEGF inhibition; • Acquired resistance to VEGF inhibition within tumor cells is reversible. Vascular endothelial growth factor (VEGF) inhibition is an essential targeted strategy for malignant tumors, but its efficacy is severely constrained by drug resistance. The traditional view holds that the target of VEGF inhibition is endothelial cells, and thus compensatory angiogenesis is considered the main mechanism of drug resistance. In this study, we found that tumor cells themselves could develop acquired resistance to VEGF therapy, indicating an independent resistance mechanism apart from angiogenesis. Notably, this acquired resistance was temporary, disappearing completely four days after discontinuing exposure to the drug in vitro. Our findings suggest that tumor cells may also be targets of VEGF inhibition, and their response to treatment should not be overlooked in contributing to drug resistance. [ABSTRACT FROM AUTHOR]