PC‐conditioned medium countered TKI effects on downstream EGFR effectors Src and Akt phosphorylation, reversible by Src or β5‐integrin inhibition/depletion, while our animal works also reveal that the co‐injection of cancer cells with PCs diminishes the efficacy of TKIs in limiting tumor burden, irrespective of their blood vessel functions, probably by repressing the inhibitory effect of TKIs on EGFR‐Src‐Akt mediated cell survival/proliferation pathways. Here, EGFR is linked to cancer.