Radiosensitivity and metastasis in squamous cell carcinoma of the head and neck: a molecular approach

In this thesis, the association between the expression of certain proteins and the outcome of radiotherapy in head and neck cancer was studied. We specifically looked at advanced tumors that were treated with surgery and received postoperative radiotherapy. The proteins selected are often deregulated in tumors. In this thesis, we focused on proteins located at a commonly amplified chromosomal region, 11q13.3, and a group of these proteins involved in the EGFR pathway, which are often deregulated and promote tumor cell survival.
Of all the proteins we studied, we found that a higher expression of pFADD was associated with lower risks of local recurrence of the tumor, while the expression of PTEN was associated with a higher risk of local recurrence.
Additionally, the same two proteins as were studied in real tumors were expressed in cell lines and then treated with radiation. This was done to investigate the mechanisms behind different outcome among patients with tumors expressing these proteins. In case of overexpression of pFADD we found that cells were more sensitive to radiation, whereas cells that overexpressed PTEN were less radiosensitive. These results would explain the clinical data.
The results of our studies show that expression of pFADD and PTEN can be used as a prognostic marker for local recurrence control in head and neck cancer patients treated with surgery and radiotherapy. Further research is needed to investigate if radiosensitivity can be improved by new agents targeted against these proteins.