PATIENT-LIKE NUDE-MOUSE AND SCID-MOUSE MODELS OF HUMAN LUNG AND PLEURAL CANCER (REVIEW)

Lung cancer is one of the leading causes of cancer-related adult deaths in the world, and its incidence is rising. Patients with malignant pleural effusions are considered to be in the advanced-stage of malignant disease or in the terminal stage. For both, the lack of efficacy of non-surgical treatment modalities is related to the lack of suitable animal models for new drug discovery. Models based on athymic nude mice have been used for human cancer research. However, s.c. or i.m. xenografts usually do not metastasize, or do so at low frequencies. Conversely, human tumor cells orthotopically implanted in the corresponding organs of nude mice result in much higher metastatic rates. By avoiding disruption of tumor integrity, we have found that orthotopic implantation of histologically-intact patient specimens leads to models better reflecting the original behavior of human cancer than models constructed by orthotopic injection of cell suspensions. With the development of a novel thoracotomy procedure, we have constructed 'patient-like' models of lung cancer (SCLC and NSCLC) with regional spread and distant metastases mimicking the clinical features of these diseases. Moreover, by implantation of histologically-intact human tumor tissue in the parietal or visceral pleura of nude mice, we were able to construct models of early- and advanced-pleural cancer, respectively. Indeed, symptoms and survival of pleural-implanted mice closely resemble the clinical situation showing a statistically-significant difference in survival between parietal- and visceral-pleural implanted mice, the latter representing an advanced-stage cancer. Thus such models, reflecting clinical features, should be of great value in the development of new drugs and treatment strategies.