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 death s in the world, and its incidence is rising. Patients with malignant p leural effusions are considered to be in the advanced-stage of maligna nt 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 mic e have been used for human cancer research. However, s.c. or i.m. xeno grafts usually do not metastasize, or do so at low frequencies. Conver sely, human tumor cells orthotopically implanted in the corresponding organs of nude mice result in much higher metastatic rates. By avoidin g disruption of tumor integrity, we have found that orthotopic implant ation of histologically-intact patient specimens leads to models bette r reflecting the original behavior of human cancer than models constru cted 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 distan t metastases mimicking the clinical features of these diseases. Moreov er, by implantation of histologically-intact human tumor tissue in the parietal or visceral pleura of nude mice, we were able to construct m odels of early- and advanced-pleural cancer, respectively. Indeed, sym ptoms and survival of pleural-implanted mice closely resemble the clin ical situation showing a statistically-significant difference in survi val between parietal- and visceral-pleural implanted mice, the latter representing an advanced-stage cancer. Thus such models, reflecting cl inical features, should be of great value in the development of new dr ugs and treatment strategies.