ABSTRACT
Malignant mesothelioma (MM) is often diagnosed late in disease progression and, at this stage, is associated with a rapid decline in health and death within a short period of time; the average period of survival being 9 months postdiagnosis. Additionally, in the absence of reliable specific tumor markers that could be utilized for early diagnosis, MM will remain undetectable until characteristic clinical symptoms manifest, which then require rigorous histopathological confirmation of disease. As a result, the tumor cell biology, as well as the specific and non-specific immune responses to MM, are difficult to monitor in humans. Hence, experimental models of MM remain the only option available to facilitate a deeper understanding of (i) how this cancer progresses in vivo, (ii) how the immune system is responding, and (iii) how we can alter tumor growth with varying single and combination therapies. This chapter will explore the experimental approaches that have been, or are being, undertaken to address features of MM development. These approaches are divided into models that utilize human-derived MM tumor cells, and environmentally (asbestos or glass fibers and/or Simian virus 40 [SV40]) induced animal MM tumor systems. Examples of the experimental models used
Examination of samples of excised tumors reveals useful information, however this approach is limited to a few technologies such as histopathology, although microarray analysis is now providing additional important data. Therefore, to gain further insights, cell lines that have been generated from human tumors and prepared as single-cell suspensions, cloned and their phenotypes, soluble factor secretion and responses to numerous agents including chemotherapeutics and gene transfer vectors, have been studied in detail. Much of this work has provided the basis of clinical trials and is the foundation for animal experimental models that are discussed in detail below.
