Inhibiting JAK2 for Inflammatory Breast Cancer

Janus kinase 2 (JAK2) inhibitors, a class of cancer drugs developed for bone marrow and blood diseases, may be promising as therapies against inflammatory breast cancer, according to research presented at the San Antonio Breast Cancer Symposium on December 7.

Often diagnosed in young women and at a late stage of progression, inflammatory breast cancer (IBC) affects 1% to 5% of breast cancer patients. “It is extremely virulent,” says Beth Overmoyer, MD, head of the Inflammatory Breast Cancer Program at Dana-Farber Cancer Institute (DFCI) and assistant professor of medicine at Harvard Medical School in Boston, who presented the work. “It's biologically very different from noninflammatory breast cancer.”

Researchers in the lab of Kornelia Polyak, MD, PhD, an associate professor of medicine and medical oncology at Harvard Medical School and DFCI, analyzed tissue samples from inflammatory breast cancer patients and discovered that more than 80% of the cells expressed the CD44⁺/CD24⁻ signature characteristic of stem cells. The STAT3/JAK2 molecular pathway was highly active in this population of cells. Polyak and her colleagues found that JAK2 inhibitors could significantly diminish the proliferation of IBC cells in vitro and also inhibit tumor growth in an IBC xenograft model.

Overmoyer's group has received funding from the Inflammatory Breast Cancer Research Foundation to investigate JAK2 inhibitors as a potential treatment for IBC in both lab work and clinical trials. (She notes that the approach could also be promising in noninflammatory triple-negative breast cancers, in which the same pathway is often active.)

Several JAK2 inhibitors are under development, and the JAK2 inhibitor ruxolitinib (Jakafi; Incyte Pharmaceuticals) was approved by the U.S. Food and Drug Administration in 2011 for treatment of myelofibrosis. The DFCI is currently leading a phase II clinical trial evaluating ruxolitinib for the treatment of advanced IBC as well as triple-negative non-IBC. Additionally, Overmoyer says, the team will launch a phase I/II study of ruxolitinib along with chemotherapy as a primary treatment of IBC. She hopes that additional research also will help clarify the biologic differences between breast cancer types.