New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

Figure 1 Notch signaling in breast cancer. In Notch-driven breast cancers, tumor cells and neighboring cells express Notch ligand and receptors. In presence of ADAM/TACE and γ-secretase enzymatic complex, Notch ligand-receptor interactions result in the release of Notch intracellular domain (NICD), which translocate to cell nucleus and activate CSL transcription factor. Target genes include signaling molecules involve in cancer cell survival, proliferation, angiogenesis, growth, energy metabolism, and chemoresistance. Inhibitors of many of these signaling molecules have been developed and are in use in various cancers, including g-secretase inhibitors, vascular endothelial growth factor inhibitors, estrogen signaling inhibitors, and HER2 inhibitors. ER: Estrogen receptor; HER2: Epidermal growth factor receptor 2; ADAM/TACE: A disintegrin and metalloprotease/tumor necrosis factor-α converting enzyme; CSL: CBF1/Suppressor of Hairless/LAG-1.