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Prognosis for breast cancer is relatively good when detected in its early stages, metastatic disease is the cause of 90 percent of all cancer-related deaths. Breast cancer patients with high levels of the protein activin-like receptor kinase (ALK1) in the blood vessels of their tumors were more likely to develop metastatic disease, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.
ALK1 expression correlated with the expression of well-known endothelial markers and that higher levels of ALK1 expression were an independent prognostic factor for poor survival in breast cancer patients. A mouse version of the ALK1 inhibitor dalantercept prevented metastatic dissemination and that combination therapy with dalantercept and the chemotherapy docetaxel was effective in preventing the spread of the primary breast tumor to the lungs.
Kristian Pietras, PhD, the Goran and Birgitta Grosskopf professor of molecular medicine at Lund University and colleagues used multiple mouse models of breast cancer; tumor samples from 768 patients in a population-based, nested case-control study; and breast cancer gene-expression data from The Cancer Genome Atlas, to understand the role of ALK1 in breast cancer metastasis and test an ALK1 inhibitor.
Pietras said, "We are investigating the role of ALK1 protein expressed by endothelial cells in promoting metastatic dissemination from primary breast tumors. The presence of high levels of ALK1 in the breast tumor vasculature is a prognostic biomarker for metastatic disease." Further, he added, "We are currently performing therapeutic studies with dalantercept in models of breast cancer in order to pinpoint the precise therapeutic regimen and disease stage at which the treatment is the most effective."
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