Epidermal growth factor receptor: a promising therapeutic target for colorectal cancer.
The epidermal growth factor receptor is a 170,000-kd transmembrane glycoprotein involved in signaling pathways affecting cellular growth, differentiation, and proliferation. An abnormal expression of the epidermal growth factor receptor (EGFR) has been described in many human tumors and implicated in the development and prognosis of malignancies, thus representing not only a possible prognostic marker, but primarily a rational molecular target for a new class of anticancer agents. The aim of this analysis is to review the available data about the biology of the EGFR and its use as a target for a new class of anticancer agents for colorectal cancer. Several clinical trials have been reported with the use of EGFR-targeted monoclonal antibodies and tyrosine kinase inhibitors, mainly in combination with chemotherapy for advanced colorectal cancer patients. Results available so far demonstrated a manageable and acceptable toxicity profile and a promising level of activity. Many critical issues are yet unresolved, such as the optimal chemotherapy regimen to combine with anti-EGFR treatment and the most adequate patient setting. Moreover, the biological selection of colorectal tumors more likely to benefit from this treatment approach is still to be defined.
Scartozzi
Mario
M
Department of Clinica di Oncologia Medica, Azienda Ospedaliera Ospedali Riuniti-Università Politecnica delle Marche, Ancona and Istituto di Anatomia Patologica, Università Politecnica delle Marche, Ancona, Italy. marioscartozzi@libero.it
Pierantoni
Chiara
C
Berardi
Rossana
R
Antognoli
Stefania
S
Bearzi
Italo
I
Cascinu
Stefano
S
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000628:therapy*; D004351:Drug Resistance / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D006801:Humans; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors