The expression of erbB-2 and epidermal growth factor receptor (EGFR) in colorectal cancers has been suggested to have diagnostic and prognostic significance.
Good correlation between H-ras expression levels and those of the upstream and downstream signaling proteins of EGFR, MEK and ERK was found, suggesting that H-ras may play a significant role in carcinogenesis of colorectal cancer.
As expression and activation levels of the epidermal growth factor receptor (EGFR) predict the metastatic potential of human colorectal cancers, the purpose of this study was to establish whether the EGF receptor tyrosine kinase (EGFR-TK) contributes to cellular invasion induced by TFFs in kidney and colonic cancer cells.
We propose that epidermal growth factor receptor-related protein inhibits cellular growth by attenuating epidermal growth factor receptor signaling processes and is an effective therapeutic agent for colorectal cancer.
Furthermore, it was demonstrated by an immunoprecipitation-western blotting analysis on 5 cases of CRC with liver metastasis that ZO-1 bound to epidermal growth factor receptor (EGFR) irrespective of the phosphorylation status of EGFR, and that EGFR associated ZO-1 was highly tyrosine-phosphorylated only in the primary CRC, but was dephosphorylated in the liver-metastasized cancers.
Overexpression of HER-2 and EGFR were observed in only a small fraction of colorectal carcinomas, but were frequently accompanied by gene amplification.
Our results suggest that the detection of the EGFR in primary colorectal cancer could be inadequate for planning therapy with EGFR-targeted monoclonal antibodies in a considerable proportion of both EGFR-positive and -negative primary tumors (36% and 15%, respectively).
More recently, novel biological agents, such as the monoclonal antibodies targeting either the epidermal growth factor receptor or vascular endothelial growth factor, have shown to provide additional clinical benefit for patients with metastatic CRC.
Criteria for cetuximab treatment in patients with HNSCC may differ from those already used for patients with colorectal carcinomas and should take different patterns of the EGFR protein overexpression into consideration.
Although the advanced clinical development of EGFR blocking drugs demonstrates their efficacy in some human metastatic diseases, such as lung, head and neck and colorectal cancers, the issue of constitutive resistance in a large number of patients and the development of acquired resistance in the responders remains an unexplored subject of investigation.
Anti-EGFR MAbs have shown antitumor activity in advanced colorectal carcinoma, squamous cell carcinomas of the head and neck, non-small-cell lung cancer (NSCLC) and renal cell carcinomas.
Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti-EGFR therapy?
Overall, our data suggest that gene polymorphisms active in the EGFR pathway may be associated with the sensitivity of colorectal cancer patients to platinum-based chemotherapy.
In searching for foundation for further investigation to optimize patient selection for cetuximab therapy, this study sought to exploit the tissue microarray and chromogenic in situ hybridization techniques to evaluate the status of epidermal growth factor receptor gene amplification in colorectal cancer and its relationship with protein expression by IHC.
Immunohistochemical profiling of colorectal cancer seems to be a promising approach, not only to define prognostic impact, but also to detail proliferation-related molecular interplays between EGFr and Cox-2 pathways, with these two latter proteins, at present, being the hottest pharmacological targets for colorectal cancer (CRC) chemoprevention and therapy.