Searching for Reliable Epidermal Growth Factor Receptor Response Predictors

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Abstract
The report by Nyati et al. in this issue (8) touches on several active research questions in the EGFR investigative field. This study examines the impact of an irreversible pan-ErbB tyrosine kinase inhibitor (CI-1033) across a series of colon cancer cell lines in vitro and in vivo. Three themes that emerge from this work warrant brief comment. First, the authors suggest that the extent of suppression of tyrosine kinase activity by CI-1033, rather than the baseline activity level before treatment, may predict for ultimate treatment efficacy. Second, the authors confirm the capacity of CI-1033 to enhance radiation response (particularly in vivo) as has been identified for several other EGFR inhibitors (Refs. 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 ; Table 1 ⇓ ). Third, the authors suggest that selected downstream signaling molecules of the EGFR pathway (in this case phospho-extracellular signal-activated kinase [ERK] 1/2) may serve as candidate markers for predicting response to ErbB inhibition. Each of these three EGFR themes remains under intense investigation within basic laboratory, translational, and clinical research programs worldwide. As of early 2004, none of these postulates has yet been definitively established within the context of mature clinical trials. However, the rapidly enlarging spectrum of trials in progress may soon allow more definitive conclusions to be drawn.

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