The development and treatment of experimental mesothelioma tumors

Pleural mesothelioma is a cancer mainly caused by exposure to asbestos. Prognosis is usually poor, due to its resistance to classical anticancer therapies. Gene therapy may represent a new hope for curing mesothelioma. I proposed to use a suicide gene system for the treatment of mesothelioma. The design consists of the transduction of herpes simplex thymidine kinase (HSVtk) gene into tumor cells. Cells expressing the HSVtk gene become sensitized to nucleotide analogs, such as gangciclovir-triphosphate, and become apoptotic and die. I used retroviral and adenoviral vectors to transduce in vitro rats and human cell lines and studied in vitro the efficiency of our system. I developed a model of pleural mesothelioma in Fischer 344 rats using syngenic cell lines. I followed up tumor progression by x-ray examination and visual inspection post-euthanasia of the animal. This model allowed in vivo testing of the suicide gene therapy system.