Metastatic spread of melanoma is associated with poor prognosis. By the time of diagnosis, metastasis to lung, liver, lymph nodes and the central nervous system are found. Thus the major cause of death for these patients is metastasis being refractive to standard therapies. In 40-60% of patients diagnosed with melanoma, brain metastases are found, often multiple foci with associated hemorrhages. Despite treatment, the median survival is less than a year.
Several causal genetic changes have been identified during the last 20 years. Mutations in cell cycle regulators such as CDKN2A/INK4a have been found, as well as mutations in various signalling molecules including NRAS, BRAF, PTEN and amplification of AKT3. Further, cell adhesion molecules (such as cadherins) are probably playing an import role in melanoma invasion.
Although we are beginning to understand tumorigenesis and the spread of systemic cancer, the key challenge is still to determine the mechanisms responsible for malignant disbursement of melanoma cells from the primary site to the brain. Providing a better insight into the signalling pathways related to metastatic spread of these tumors, may lead to new therapeutic targets and better anticancer strategies. For this purpose we have now developed more appropriate animal models to study melanoma metastasis, using human melanoma cells. Brain metastases from melanoma patients have been put into cell culture, and we have been able to develop several human melanoma cell lines that are tumorigenic when injected intracardially into immunodeficient mice. The development of the model systems, as well as results on molecular and radiological characterization of metastatic tumor spread in the models will be presented.
When: 10/27/11 4:00 PM
Where: 1005 GBSF