Melanoma clinical outcomes in patients correlate with xenograft models
An innovative model has been developed to predict the progression of melanoma in patients. Stage III human melanoma cells from 20 patients were implanted into specially selected mice with compromised immune systems. This xenograft model allowed the research team to observe reproducible differences in the rate at which the cancer metastasized in the mice that correlated with clinical outcomes in the patients.
Previous studies of cancer metastasis have been limited by a lack of workable models in which scientists could study the progression of a patient's cancer cells in laboratory animals in a way that correlated with clinical outcomes. This xenograft model will make it possible to study the mechanisms that regulate disease progression and distant metastasis of melanomas in patients. The researchers hope their system will lead to new prognostic markers that identify both the patients at the highest risk of disease progression and also new therapies.
Those human melanomas that metastasized efficiently in the mice gave rise to circulating melanoma cells in the blood of the mice, and eventually progressed to advanced, stage IV disease in the patients. When the melanoma did not metastasize efficiently in the mice, it also did not form distant metastases in the patients within 22 months. The finding of circulating melanoma cells suggests that the entry of melanoma cells into the blood is a step that limits the rate of distant metastasis.
“We believe this is the only time in cancer biology that anyone has developed a xenograft model in which disease progression correlates with what happens in the patient,” said senior author Sean Morrison, PhD, of the Children's Medical Center Research Institute at UT Southwestern. “The highly immune-compromised state of the mice makes it possible to observe the metastasis of human melanomas, and to study intrinsic differences among melanomas in their metastatic potential.”
“Ultimately we want to identify new drug targets,” Dr. Morrison said. “There are promising ideas coming out of this work that we hope will lead to clinical trials in melanoma.”This study was published in Science Translational Medicine (2012; doi:10.1126/scitranslmed.3004599).