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.
METHODS:
Gefitinib ("
Iressa,"
ZD1839), a small molecule EGFR
tyrosine kinase inhibitor, can inhibit the proliferation of OSCC cell lines in a dose- and time-dependent 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-activated 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-2 expression correlated inversely with increased
tumor radiation sensitivity. Treatment with
celecoxib, a COX-2 selective inhibitor, enhanced the radioresponsiveness of HSC-2 cells, which constitutively expressed COX-2. Another promising molecular target is the
PPARgamma, which is a member of the
nuclear receptor superfamily of
ligand-activated
transcription factors. Recent studies have demonstrated that
PPARgamma ligands induce cellular differentiation and inhibit cell growth in
carcinomas of various types. These data suggest that synthetic
PPARgamma 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.
CONCLUSION: 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.