Familial Nasopharyngeal Carcinoma 6

Molecular Signaling Pathways 3in Nasopharyngeal CancerQuynh-Thu Le and Jiade J. LuCONTENTS3.1 Introduction 273.2 Epidermal Growth Factor Receptor andNasopharyngeal Carcinoma 283.2.1 Epidermal Growth Factor Receptor 283.2.2 EGFR Ligands and the EffectorPathways 293.2.3 Interactions Between EGFR SignalingPathways and Radiotherapy 293.2.4 EGFR in Nasopharyngeal Carcinoma 303.2.5 Targeting EGFR for Nasopharyngeal CancerTreatment 323.3 Angiogenesis and NasopharyngealCarcinoma 323.3.1 Angiogenesis 323.3.2 Vascular Endothelial Growth Factorsand Receptors 333.3.3 Angiogenesis in Nasopharyngeal Cancer 343.3.4 Targeting VEGF and VEGFRin Nasopharyngeal Cancer Treatment 353.4 Wnt Pathway in NPC 363.5 MicroRNA in NPC 363.6 Summary 37References 38Quynh T. Le, MDDepartment of Radiation Therapy, 875 Blake Wilbur Dr,MC 5847, Stanford, CA 94350-5847, USAJiade J. Lu, MD, MBADepartment of Radiation Oncology, National University CancerInstitute, National University Health System, National Universityof Singapore, 5 Lower Kent Ridge Road, Singapore 119074,Republic of Singapore3.1IntroductionNasopharyngeal carcinoma (NPC) is a unique typeof head and neck malignancy that shows a clearregional and racial prevalence. It occurs most commonlyin Asians who inhabit in the Southern Chineseprovinces and Southeast Asia (Ma and Cao 2009).The biological behavior of NPC differs significantlyfrom other types of squamous cell carcinoma of thehead and neck, which are abbreviated here as SCCHN:NPC has the highest propensity of regional and distantmetastases when compared with SCCHN. At thesame time, NPC is more sensitive to ionizing radiationand chemotherapy.The underlying reason for the differences in thebiologic and clinical behaviors between NPC andother head and neck malignancies is of particularinterest. One underlying factor mediating the biologicalbehavior of a malignancy is the mechanismstransmitting the extracellular signals to the intracellularcompartments. Such signaling pathways arecritical for cell survival, growth, and metastasis. Betterunderstanding of the molecular signaling path waysin SCCHN has provided a substantial opportunity fornovel and individualized treatment in patients withthese cancers. For example, the epidermal growth factorreceptor (EGFR), which mediates multiple cellularprocesses including proliferation, survival, and angiogenesis,has been found to be highly expressed inSCCHN and is associated with worse prognosis inthese tumors (Ang et al. 2002). Therefore, studieswere conducted to target this pathway in combinationwith either radiation or chemotherapy in patientswith locally advanced or metastatic SCCHN (Bonneret al. 2006; Vermorken et al. 2008). These studieshave shown that EGFR targeting could enhance theeffect of traditional therapies and resulted in improvedsurvival in these patients. In addition to the EGFR