ELENA TASSI and ANTON WELLSTEIN
Lombardi Cancer Center Georgetown University Washington, DC 20007
I. Epidemiology, Pathology, and Biology of Head and Neck Squamous Cell Carcinoma (HNSCC) 81
II. Basic Mechanisms of Angiogenesis 82
A. General Concepts 82
B. Mechanisms of Tumor Angiogenesis 83
C. Tumor Angiogenesis: The Angiogenic Switch 83
III. Angiogenesis in HNSCC 83
A. Clinical Evidences 83
B. Angiogenic Factors in HNSCC 85
IV. Antiangiogenic Therapies in HNSCC 91
In the past few years, tumor angiogenesis has been correlated to the progression and metastasis of different human tumors. Several studies have been performed in the attempt to define how angiogenesis contributes to the progression of head and neck squamous cell carcinoma (HNSCC). This review gives further insights into the understanding of the correlation between angiogenesis and HNSCC tumorigenesis. Analysis of the general mechanisms of tumor angiogenesis, clinical evidences, and the function of distinct proangiogenic factors involved in HNSCC tumor progression, in addition to the current antiangiogenic therapies, are discussed.
I. EPIDEMIOLOGY, PATHOLOGY, AND BIOLOGY OF HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC)
Head and neck cancers encompass a diverse group of uncommon tumors that are frequently aggressive in their biological behavior. The vast majority (95%) of head and neck tumors are squamous cell carcinomas (HNSCC), the most common type of cancer affecting the lining of the airways and upper digestive organs. HNSCC comprises a wide variety of epithelial malignant lesions affecting the nasal cavity and paranasal sinuses, nasopharynx, oral cavity, lips, alveolar ridge and retromolar trigone, floor of the mouth, tongue, hard and soft palat, tonsil, pharyngeal wall, larynx, hypopharynx, and salivary glands. Cancer in these locations originates from the cuboidal cells along the basement membrane of the mucosa and usually has profound impairing effects on breathing, speaking, and swallowing. The disease is characterized by local tumor aggressiveness, early recurrence, and high frequency of second primary tumors. Neoplasias of the head and neck region are relatively infrequent in comparison with cancer occurring in the breast, lung, prostate, and colon and represent approximately 5.6% of all tumors. However, nearly 46,000 new cases of head and neck cancer are diagnosed every year in the United States. It is more frequent in men, by a ratio of 5:1, but an increasing percentage is occurring in women. Moreover, the incidence increases with age, especially after the fifth or sixth decade. The occurrence of HNSCC correlates most closely with the use of tobacco. Alcohol consumption, by itself, has been proved to be a risk factor for the development of pharyngeal and laryngeal tumors, although is a less potent agent than tobacco. In addition, the abuse of both alcohol and tobacco appears to have a synergistic effect for HNSCC development and results in a multiplicative increase in risk. Other risk factors, such as ultraviolet light, radiation exposure, and viruses (Epstein-Barr virus, papilloma virus, herpes simplex virus), are associated with development of the HNSCC. Tumorigenesis can be viewed as results of a complex "yin-and-yang" balance of
Head and Neck Cancer
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