الفهرس 
Introduction and aim of the work
Aim of the workOnly 14 pages are availabe for public view
 |  | from | 106 |  |  |
| | | from | 106 | | |
Abstract
Worldwide, CRC is the 4th most common cancer in males and the 2nd in females. In Egypt, it is the 4th most common cancer in both males and females. It has several risk factors with complex interactions between age, genetic and environmental changes. Macroscopically, CRC may be early (protruded, flat or ulcerated) or advanced (polypoid, ulcerating or diffusely infilterating). Histopathologically, it is classified according to WHO into: adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, small cell carcinoma, squamous cell carcinoma, adenosquamous carcinoma, medullary carcinoma and undifferentiated carcinoma. Various other histological variants are also present. Many classifications were developed for CRC staging, including Dukes’, Astler-Collar and TNM staging systems. EGFR is a member of a family of transmembrane protein kinase receptors known as the erbB or HER receptor family. It consists of three domains: an extracellular ligand-binding domain, a hyDROPhobic transmembrane domain and an intracellular domain with tyrosine kinase activity. EGFR is expressed in many epithelial tumors including CRC, in which high level of expression is associated with aggressive disease, poor prognosis and decreased survival. Unfortunately, the rate of overexpression of EGFR in primary CRC and its metastasis measured by either IHC or FISH varies widely, probably due to lack of a uniform and standardized method for both, yielding EGFR overexpression in CRC a controversial prognostic factor. Recently, there has been considerable interest in developing new agents that specifically target EGFR to improve the outcome of CRC patients. Among these drugs, cetuximab is the most advanced anti-EGFR antibody in clinical development. Unfortunately, poor correlation was observed between EGFR expression and the clinical outcome of cetuximab therapy. So, EGFR IHC and FISH analysis don’t seem to be sufficient tests for selecting candidate CRC patients for anti-EGFR therapy. Moreover, many CRC patients develop resistence to these agents due to several genetic and epigenetic mechanisms. Understanding this could lead to more effective therapies. Many challenges face the current use of EGFR-directed therapy.