BioCentury
ARTICLE | Distillery Therapeutics

Cancer

March 8, 2017 2:58 PM UTC

Patient sample and mouse studies suggest inhibiting the CD109-JAK-1-STAT3 axis could help treat metastatic lung cancer. In patients, high levels of CD109 in primary tumors correlated with poor overall survival. In multiple mouse and human metastatic lung cancer cell lines, knockdown of CD109 decreased clonal growth and migration compared with normal CD109 expression. In one of the mouse cell lines, knockdown of STAT3 or JAK-1 decreased clonal growth and migration compared with normal STAT3 and JAK-1 expression. In three mouse models and a xenograft mouse model of metastatic lung cancer, CD109 knockdown decreased lung metastasis compared with normal CD109 expression. In one of the models, knockdown of STAT3 or JAK-1, the JAK-1/JAK-2 inhibitor Jakafi ruxolitinib or the JAK-1 inhibitor filgotinib decreased lung metastasis compared with normal STAT3 and JAK-1 expression or vehicle. In the xenograft model, a pan-JAK inhibitor tool compound decreased lung metastasis compared with vehicle. Next steps could include identifying and testing CD109 inhibitors in models of metastatic lung cancer.

Incyte Corp. and Novartis AG market Jakafi to treat myeloproliferative disorder and have the compound in Phase II testing to treat breast cancer, metastatic colorectal cancer, leukemia and graft-versus-host disease (GvHD)...