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About the Authors:
Tapan K. Nayak
* E-mail: [email protected] (TKN); [email protected] (MWB)
Affiliation: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America
Kayhan Garmestani
Affiliation: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America
Diane E. Milenic
Affiliation: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America
Kwamena E. Baidoo
Affiliation: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America
Martin W. Brechbiel
* E-mail: [email protected] (TKN); [email protected] (MWB)
Affiliation: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America
Introduction
Asbestos-related deaths have increased 400 percent in the past 20 years and the number of cases continues to increase despite awareness of asbestos-related hazards [1], [2]. Asbestos is a human mutagen and carcinogen, responsible for many pulmonary diseases including asbestosis, bronchogenic carcinoma, and malignant mesothelioma [2]. Malignant mesothelioma (MM) is a rare form of an aggressive and often treatment-resistant cancer [3]. Occupational exposure to asbestos is implicated in 70–80% of all MM. After initial diagnosis, MM has a median survival of 10–18 months [3], [4]. Conventional therapies, such as surgery, radiotherapy, and chemotherapy, do not necessarily improve overall survival. On the other hand, tremendous advances have been made regarding understanding the molecular biology of MM.
Understanding the molecular biological features of asbestos-induced MM is of critical importance. MM cells arise from the pleura or the peritoneal cavity and produce numerous growth factors, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and transforming growth factor β (TGF-β) [3], [5], [6]. EGF is a potent mitogen for human mesothelial cells. In normal and pre-malignant animal cells of similar type, exposure to asbestos leads to autophosphorylation, increased expression of the cell surface EGF receptor (HER1) that then appears to initiate cell signaling cascades important in asbestos-induced mitogenesis and carcinogenesis [7], [8], [9].
Recent clinical studies have also shown over-expression of HER1 in MM [10], [11], [12], [13]. In an immunohistochemical (IHC) and molecular study with clinico-pathological correlations,...