As a heterogeneous disease,
breast cancer (BC) has been characterized by the uncontrolled proliferation of mammary epithelial cells.The tumor microenvironment (TME) also contains inflammatory cells, fibroblasts, the
extracellular matrix (ECM), and soluble factors that all promote BC progression. In this sense, the macrophage migration inhibitory factor (MIF), a pleiotropic pro-inflammatory cytokine and an upstream regulator of the immune response, enhances breast tumorigenesis through escalating cancer cell proliferation, survival, angiogenesis, invasion, metastasis, and stemness, which then brings tumorigenic effects by activating key oncogenic signaling pathways and inducing immunosuppression.The TME has emerged as a key factor in the pathogenesis of BC. The pro-inflammatory cytokine, MIF, which is part of this environment, accordingly increases breast tumorigenesis by augmenting cancer cell proliferation, survival, angiogenesis, invasion, metastasis, and stemness. Studies have thus far established that the
MIF expression in BC tissues is much higher than that in the normal ones, and this overexpression indicates a poor prognosis in patients with BC. Research on targeting the
MIF using various inhibitors, such as small molecules, Abs, or siRNA have further shown good results, such as a reduction in breast tumor growth and metastasis.Current therapeutic strategies to target the
MIF are also mainly focused on the development of small inhibitors of its tautomerase or biological activities, as discussed in detail .Due to the upstream role of
MIF in coordinating TME and tumorigenesis in BC, the use of these inhibitors with effects, such as apoptosis and cell death, cell proliferation inhibition, angiogenesis, and metastasis can be taken into account as an appropriate therapeutic strategy to inhibit the
MIF signaling. In view of this, experimental studies on the
MIF inhibitors seem to be promising and lead to longer patient survival and better prognosis in BC. Therefore, the
MIF is a valuable therapeutic target in BC, and further evaluation of the MIF-based combination regimens, eg, combining a potent
MIF inhibitor with any of the promising chemotherapy and immunotherapy options in clinical trials, can be beneficial for these patients with limited treatment options.