Scartozzi M et al. (2007) Epidermal growth factor receptor (EGFR) downstream signalling pathway in primary colorectal tumours and related metastatic sites: optimising EGFR-targeted treatment options. Br J Cancer 97: 92–97

Investigations have shown that EGFR status is not predictive of success with anti-EGFR therapies in colorectal cancer. Scartozzi et al. studied EGFR status and expression of the EGFR downstream kinases phosphorylated Akt and MAPK in primary colorectal tumors and their corresponding metastatic sites in order to define the EGFR-regulated molecular profile that would aid treatment selection.

The findings indicate that Akt and MAPK expression could be independent of EGFR status in both the primary and metastatic sites. A high proportion of EGFR-negative primary tumors stained positive for phosphorylated Akt or MAPK (75% for both), while many EGFR-positive primary colorectal cancers stained negative for phosphorylated Akt or MAPK (25% and 30%, respectively). Similarly, 73% and 64% of EGFR-negative metastatic samples were positive for phosphorylated Akt and MAPK, respectively, and 31% and 22% of EGFR-positive metastatic samples were negative for phosphorylated Akt and MAPK, respectively. Furthermore, Akt and MAPK status was frequently different between the primary and the corresponding metastatic sites, with 13–16% of all sites changing from positive to negative and 12–13% of all sites from negative to positive—a phenomenon that could possibly explain the failure of anti-EGFR therapy in some patients.

The authors suggest that tyrosine kinase inhibitors targeted downstream of the EGFR signaling pathway could theoretically prove more effective than anti-EGFR treatment in this cancer. Prospective trials will confirm whether the hypotheses made on the basis of this study's findings are correct.