Researchers at the University of Michigan (UM) Comprehensive Cancer Center hope to start clinical trials next year evaluating an approach to breast cancer therapy that combines an IL-6 inhibitor with Herceptin (Roche’s humanized antibody therapy trastuzumab). Nearly half of Her2-positive breast cancers are resistant to Herceptin, and those that are initially responsive to the drug will eventually become resistant. The UM scientists have now found that breast cancer cells can switch on an inflammatory pathway involving IL-6 that propagates tumor cell growth independently of Her2.
Most notably, their work, to be published in next month’s issue of Molecular Cell, indicated that the IL-6 pathway promotes the development of cancer stem cells (CSCs), which are responsible for breast cancer metastasis and aggressiveness. Blocking IL-6 thus markedly reduced numbers of these cells. Moreover, mice with newly developing tumors remained sensitive to Herceptin when they were treated with an IL-6 inhibitor in addition to the Herceptin.
Roche’s IL-6 inhibitor RoActemra/Actemra (tocilizumab) is an IL-6 blocker already marketed for the treatment of rheumatoid arthritis. “What we’ve found now is that in many of the Herceptin-resistant breast cancers the IL-6 inflammation loop is driving the cancer stem cell,” explains lead study author Hasan Korkaya, Ph.D., research assistant professor of internal medicine at the UM Medical School.
There’s already evidence that patients with high levels of IL-6 have a poorer prognosis, adds Max S. Wicha, M.D., senior study author and distinguished professor of oncology and director for the UM Comprehensive Cancer Center. “Our study suggests that an IL-6 inhibitor in combination with Herceptin may be a valuable addition for treating Her2-positive breast cancer.”
The UM teams' work will be detailed in a paper titled “Activation of an IL-6 Inflammatory Loop Mediates Trastuzumab Resistance in Her2+ Breast Cancer by Expanding the Cancer Stem Cell Population.”