Shinichiro Kashiwagi1, Yuka Asano2, Wataru Goto2, Koji Takada2, Katsuyuki Takahashi3, Takaharu Hatano4, Sayaka Tanaka5, Tsutomu Takashima2, Shuhei Tomita3, Hisashi Motomura4, Masahiko Ohsawa5, Kosei Hirakawa2, Masaichi Ohira2. 1. Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan spqv9ke9@view.ocn.ne.jp. 2. Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. 3. Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4. Department of Plastic and Reconstructive Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 5. Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Abstract
BACKGROUND/AIM: Eribulin mesylate (eribulin) is currently used for the treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress the epithelial-mesenchymal transition (EMT) of cancer cells and promote tumor vascular remodeling. In this study, we investigated the expression of markers for EMT and hypoxia in sets of clinical specimens collected before and after eribulin treatment to verify its unique mechanisms. PATIENTS AND METHODS: The expression of markers for EMT and cellular hypoxia [E-cadherin, N-cadherin, vimentin, and carbonic anhydrase 9 (CA9)] was examined immunohistochemically in MBC tissues collected from 20 patients before and after chemotherapy with either eribulin (n=10) or paclitaxel (n=10). RESULTS: An increase of E-cadherin and decrease of CA9 expression were observed in MBC tissues from patients with objective clinical responses to eribulin treatment. Patients with E-cadherin-positive conversion and CA9-negative conversion had significantly higher response rates (p=0.004 and p=0.024, respectively) and prolonged time to treatment failure (p=0.018 and p=0.038, respectively) than patients without changes in marker expression. CONCLUSION: Expression of EMT and hypoxia markers in clinical samples from patients with MBC was suppressed by eribulin treatment. The results provide additional clinical data on improved survival of patients treated with eribulin and the mechanism of response. Copyright
BACKGROUND/AIM: Eribulin mesylate (eribulin) is currently used for the treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress the epithelial-mesenchymal transition (EMT) of cancer cells and promote tumor vascular remodeling. In this study, we investigated the expression of markers for EMT and hypoxia in sets of clinical specimens collected before and after eribulin treatment to verify its unique mechanisms. PATIENTS AND METHODS: The expression of markers for EMT and cellular hypoxia [E-cadherin, N-cadherin, vimentin, and carbonic anhydrase 9 (CA9)] was examined immunohistochemically in MBC tissues collected from 20 patients before and after chemotherapy with either eribulin (n=10) or paclitaxel (n=10). RESULTS: An increase of E-cadherin and decrease of CA9 expression were observed in MBC tissues from patients with objective clinical responses to eribulin treatment. Patients with E-cadherin-positive conversion and CA9-negative conversion had significantly higher response rates (p=0.004 and p=0.024, respectively) and prolonged time to treatment failure (p=0.018 and p=0.038, respectively) than patients without changes in marker expression. CONCLUSION: Expression of EMT and hypoxia markers in clinical samples from patients with MBC was suppressed by eribulin treatment. The results provide additional clinical data on improved survival of patients treated with eribulin and the mechanism of response. Copyright