{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:33:37Z","timestamp":1791282817920,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,4,21]],"date-time":"2008-04-21T00:00:00Z","timestamp":1208736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recently, attention has been focused on molecular targeted cancer therapy in various tumors. Although there is no single consistent molecular target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer (SGC), there are a number of promising candidate proteins. The aim of this review is to introduce the basic evidences to support the molecular targeting for OSCC and SGC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We focused on the 4 molecules, epidermal growth factor receptor (EGFR), cyclooxygenase\u20102 (COX\u20102), peroxisome proliferator\u2010activated receptor \u03b3 (PPAR\u03b3), and progesterone receptor, that are, respectively, associated with the proliferation and the differentiation of OSCC and SGC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gefitinib (\u201cIressa,\u201d ZD1839), a small molecule EGFR tyrosine kinase inhibitor, can inhibit the proliferation of OSCC cell lines in a dose\u2010 and time\u2010dependent manner and lead to cell cycle arrest with accumulation of cells in the G1 phase, and a decrease of cells in S phase. The agent suppressed tumor metastasis in the animal model. Furthermore, a cooperative antiproliferative effect was obtained when cancer cells were treated with radiation followed by gefitinib. While radiation alone did not significantly affect p38 mitogen\u2010activated protein kinase and MAP kinase kinase (MEK)1\/2 autophosphorylation, the combination of gefitinib and radiation completely inhibited the downstream signaling of EGFR. Gefitinib enhanced tumor radioresponsiveness by multiple mechanisms, including the growth inhibition and effects on DNA repair after exposure to radiation. Next, the level of COX\u20102 expression correlated inversely with increased tumor radiation sensitivity. Treatment with celecoxib, a COX\u20102 selective inhibitor, enhanced the radioresponsiveness of HSC\u20102 cells, which constitutively expressed COX\u20102. Another promising molecular target is the PPAR\u03b3, which is a member of the nuclear receptor superfamily of ligand\u2010activated transcription factors. Recent studies have demonstrated that PPAR\u03b3 ligands induce cellular differentiation and inhibit cell growth in carcinomas of various types. These data suggest that synthetic PPAR\u03b3 ligands may be useful for molecular targeting of oral cancer. Finally, the possibility of using molecular targeted therapy directed at hormone receptors in the treatment of advanced SGCs was described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The basic data strongly suggested the possibility of tumor suppression by targeting these molecules. Studies of different targeted agents alone or with more conventional treatment modalities are needed to fully determine what role the targeted therapy will play in the management of patients with OSCC and SGC. \u00a9 2008 Wiley Periodicals, Inc. 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