Issues

The work by Poindessous and colleagues shows that inhibition of EGFR- and VEGF(R)-signaling by combinations of two small molecule tyrosine kinase inhibitors (TKI), afatinib and vargatef, has synergistic activity in colorectal cancer models that are refractory to combinations of the monoclonal antibodies cetuximab and bevacizumab. Importantly, only the TKIs were able to attenuate the phosphorylation of intracellular EGFR- and VEGFR-receptors which was accompanied by the induction of apoptotic cell death as indicated by TUNEL staining (nuclear DNA in blue, apoptotic nuclei in white). This work provides a rationale for clinical trials of the afatinib and vargatef combination, even in patients with mutant KRAS. For details, see the article by Poindessous and colleagues on page 6522 of this issue.