The epithelial growth factors, EGF and TGF-alpha, which share the same receptor, EGFR, may play a pivotal role in the development and maintenance of head and neck cancer; preliminary studies concerning TGF-beta and IL-2 are inconclusive.
Increased production of TGF-alpha and EGFR mRNA in the histologically normal mucosa of patients at risk for a primary or secondary head and neck cancer may serve both as a marker for malignant transformation and as a target for preventive therapies.
These experiments indicate that EGFR gene expression and function is critical for SCCHN cell growth but not for growth of normal mucosa cells and therefore may serve as a tumor-specific target for preventive and therapeutic strategies in head and neck cancer.
Protein localization studies showed that TGF-alpha and EGFR are produced by the same epithelial cells in tissues from head and neck cancer patients further supporting a role for this ligand-receptor pair in an autocrine growth pathway.
These results suggest that the cisplatin sensitivity of head and neck cancer cells corresponds to subsequent alteration of EGFR levels following cisplatin treatment.
The CK19 expression was found in 36/47 patients (9 colorectal, 9 head and neck and 18 breast cancer), two patients (one affected by colorectal and one by head and neck cancer) were positive for CK20 whereas EGFR was found expressed in 9 patients (3 colorectal, 5 head and neck and one breast cancer).
New drugs, including those that target the epidermal growth factor receptor, the p53 gene, RAS protein post-translational modification, the proteosome, vascular endothelial growth factor, cyclooxygenase-2 and other molecular pathways, are promising agents in the management of head and neck cancer.
The authors focus especially on molecular markers evaluated for association with clinical response and include data from EGFR-targeted clinical studies in other cancer sites that they anticipate will be of interest to the head and neck cancer research and treatment communities.
This has led to the question of whether EGFR remains a viable target in patients other than those whose tumors contain mutations, and whether the modest activity of cetuximab in colorectal cancer and head and neck cancer represents all that we can expect from inhibition of this pathway in the absence of mutation.
Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefit in colorectal and head and neck cancer when combined with chemotherapy and/or radiation.
Another receptor tyrosine kinase, the epidermal growth factor receptor (EGFR), is an established therapeutic target in head and neck cancer and IGF-IR/EGFR heterodimerization has been reported in other epithelial cancers.
However, in vitro observations of synergy between EGFR inhibitors and radiation therapy have been confirmed in the clinical setting of head and neck cancer.
Intratumoral epidermal growth factor receptor antisense DNA therapy in head and neck cancer: first human application and potential antitumor mechanisms.