To target aberrant signalling through EGFR, monoclonal antibodies were the first approach to be investigated. Laboratory studies with murine monoclonal antibodies MAb 528 and MAB 225 demonstrated high affinity. IMC 225 1, was the first antibody for clinical use that binds to extra cellular domain of EGFR and blocks the binding of activating ligands like EGFR and TGF-α. This inhibits autophosphorylation of receptor, induces internalisation of receptor and degradation of EGFR. This also causes p 27 inhibition and G₁ cell cycle arrest.

The second antibody to be tested was ABX-EGF, which is a human immunoglobulin G2 monoclonal antibody. The mechanism of action is similar to that of IMC-225, however being completely human it does not produce immunogenic response against antibody, which improves efficacy and reduces premature termination of treatment due to side effects. Its safety has been demonstrated in phase I studies 2345.

An alternate strategy is to inhibit EGFR TK activity using small molecules 6, like ZD 1839 (gefitinib, 'Iressa™'; Astra Zeneca) approved for use in lung cancer 71 and several such other molecules like OSI-774, CI-1033 (PD 183805) and PKI-166 have been evaluated in phase I and II trials while several others like EKB – 569, PD 168393, GW 2016 and CGP 59326 are in pre-clinical trials. These molecules act by inhibiting EGFR-TK thus inhibiting autophosphorylation of EGFR 83.

The dream of inhibiting EGFR for its potential clinical use has become a reality. The day is not for when anti EGFR strategies will become another arrow in the quiver of anticancer armamentarium of clinical oncologists.