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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01138

Cabozantinib (XL184) and R428 (BGM324) inhibit the growth of esophageal squamous cell carcinoma (ESCC)

Pei-Wen Yang1,  Yu-Cheng Liu1,  Ya-Han Chang1, Ching-ching Lin1, Pei-Ming Huang1, Kuo-Tai Hua1,  Jang-Ming Lee1* and  Min-Shu Hsieh1*
  • 1National Taiwan University Hospital, Taiwan

Esophageal squamous cell carcinoma (ESCC) is a deadly disease for which no effective targeted therapeutic agent has been approved. Both AXL and c-MET have been reported to be independent prognostic factors for ESCC. Thus, inhibitors of AXL/c-MET might have great potential as targeted therapy for ESCC. In the current study, we evaluated the therapeutic potential of the AXL/c-MET selective inhibitors, R428 and cabozantinib, in cell and mouse xenograft models. We demonstrated that both R428 and cabozantinib significantly inhibited the growth of CE81T and KYSE-70 ESCC cells and showed by wound-healing assay that they both inhibited ESCC cell migration. In the animal model, ESCC xenograft models were established by injecting KYSE70 cells with matrigel into the upper back region of NOD-SCID male mice followed by treatment with vehicle control, R428 (50 mg/kg/day), cisplatin (1.0 mg/kg) or cabozantinib (30 mg/kg/day) for the indicated number of days. R428 alone significantly inhibited ESCC tumor growth compared to the vehicle; however, no synergistic effect with cisplatin was observed. Notably, the dramatic efficacy of cabozantinib alone was observed in the mice xenograft model. Collectively, our study demonstrated that both cabozantinib and R428 inhibit ESCC growth in cell and xenograft models. The results reveal the great potential of using cabozantinib for targeted therapy of ESCC.

Keywords: Esophageal cancer (EC), Esophageal squamous - cell carcinoma, Cabozanitinb, R428, targeted therapy

Received: 06 Mar 2019; Accepted: 11 Oct 2019.

Copyright: © 2019 Yang, Liu, Chang, Lin, Huang, Hua, Lee and Hsieh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Jang-Ming Lee, National Taiwan University Hospital, Taipei, 100, Taiwan, jmlee@ntu.edu.tw
Prof. Min-Shu Hsieh, National Taiwan University Hospital, Taipei, 100, Taiwan, mshsieh065@gmail.com