Epidermal Growth Factor Receptor–Vascular Endothelial Growth Factor pathway cross-talk (EGFR–VEGF cross-talk)

The EGFR–VEGF pathway cross-talk refers to the complex reciprocal signaling relationship between the Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor (VEGF) systems, which together drive tumor growth and progression (Ciardiello et al., 2006). EGFR signaling in tumor cells can directly stimulate the production of VEGF, promoting angiogenesis, while VEGF/VEGFR signaling in the tumor microenvironment can provide survival signals that bypass EGFR inhibition, contributing to acquired resistance (Larsen et al., 2011). This interaction is a critical mechanism in various malignancies, particularly non-small cell lung cancer (NSCLC) and colorectal cancer, where single-pathway inhibition often fails due to compensatory activation of the other (Tabernero, 2007). Therapeutic strategies targeting this cross-talk include the use of multi-kinase inhibitors that hit both EGFR and VEGFR or the combination of specific monoclonal antibodies and small-molecule inhibitors. By simultaneously disrupting both the proliferative and angiogenic axes, these therapies aim to achieve more durable clinical responses and overcome resistance, though they also present cumulative safety challenges such as concurrent hypertension and severe skin toxicity (NIH/NCI).

Other names

EGFR-VEGF signaling axisEGFR-VEGFR interactionDual EGFR/VEGF inhibition targetEGFR-VEGF reciprocal signaling

Dual inhibition of EGFR-mediated intracellular signaling (MAPK/PI3K) and VEGF-mediated angiogenic signaling to disrupt tumor cell survival and the supporting microenvironment (Ciardiello et al., 2006).