Therapeutics: Janus kinase-2 (JAK-2)
Patient sample, cell culture and mouse studies suggest JAK-2 inhibitors could help treat a subset of triple-negative breast cancer (TNBC) patients who receive neoadjuvant chemotherapy. In 7 out of 74 TNBC patients, neoadjuvant chemotherapy increased tumor levels of JAK-2 compared with pretreatment baselines, and in those patients, JAK-2 levels correlated with poor recurrence-free survival and overall survival. In 2 out of 22 patient-derived xenograft mouse models of TNBC, chemotherapy increased tumor levels of JAK-2 compared with pretreatment baselines. In human TNBC cell lines pretreated with the generic chemotherapy paclitaxel, shRNA targeting JAK-2 or a JAK-2 inhibitor tool compound decreased colony formation compared with scrambled shRNA or vehicle. In a paclitaxel-treated xenograft mouse model of TNBC, the JAK-2 inhibitor decreased tumor growth compared with vehicle. Next steps could include testing JAK-2 inhibitors in breast cancer models treated with other neoadjuvant chemotherapies.
Incyte Corp. and Novartis AG market Jakafi ruxolitinib, an oral JAK-1 and JAK-2 inhibitor, to treat myeloproliferative disorder and have the compound in Phase II testing to treat breast cancer, metastatic colorectal cancer (mCRC) and leukemia. ...