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Targeting AXL Using the AVB-500 Soluble Receptor and through Genetic Knockdown Inhibits Bile Duct Cancer Growth and Metastasis

Authors
 Jiyoung Kim  ;  Gilyeong Nam  ;  You Keun Shin  ;  Nuria Vilaplana-Lopera  ;  Hei-Cheul Jeung  ;  Eui Jung Moon  ;  Ik Jae Lee 
Citation
 CANCERS, Vol.15(6) : 1882, 2023-03 
Journal Title
CANCERS
Issue Date
2023-03
Keywords
AVB-500 ; AXL ; bile duct cancer ; invasion ; metastatsis
Abstract
Simple Summary Bile duct cancer (cholangiocarcinoma) is a relatively rare cancer type that has a 5-year survival rate of 26% if diagnosed early, but a survival rate of less than 10% if the cancer has spread to the lymph nodes. Most patients with bile duct cancer are treated with surgery and chemotherapy, which unfortunately is more palliative than curative. In comparison to other gastrointestinal cancers, there are few targeted therapies which are specific to bile duct cancer. In searching for new molecular targets for bile duct cancer diagnosis and therapy, we found that the receptor tyrosine kinase AXL is highly expressed in bile duct cancer cells and that inhibition of its expression and signaling significantly reduces tumor growth and the spread of cancer cells. This study suggests that AXL is a potential new therapeutic target for treating bile duct cancers. Bile duct cancer, or cholangiocarcinoma, is a rare disease with limited treatment options that include surgery and cytotoxic chemotherapy. The high recurrence rate and poor prognosis of this type of cancer highlights the need to identify new and more effective therapeutic targets. In this study, we found that AXL, a receptor tyrosine kinase, is highly expressed in biliary cancer patients and significantly correlated with poor patient outcomes, including metastasis and low survival rates. We also demonstrated that targeting AXL inhibits tumor progression. In vitro studies with bile duct cancer cells (SNU1196 and HUCCT1) showed that genetic knockdown of AXL significantly reduced both tumor cell growth and invasion. In addition, in vivo studies using subcutaneous and orthotopic intrahepatic models demonstrated that genetic inhibition of AXL resulted in tumor-growth delay. To further examine the possible clinical translation of AXL inhibition in the clinic, we tested the efficacy of AVB-500, a soluble AXL receptor, in reducing AXL activation and tumor growth. AVB-500 was effective at inhibiting AXL activation and decreasing the growth and invasion of SNU1196 and HUCCT1 tumors which possess high AXL expression. Most importantly, AVB-500 was highly effective at decreasing tumor dissemination of bile duct tumor cells in the peritoneal cavity. This study strongly supports the idea of using the AXL receptor as a new therapeutic target to treat the growth and progression of biliary cancer.
Files in This Item:
T202302632.pdf Download
DOI
10.3390/cancers15061882
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Lee, Ik Jae(이익재) ORCID logo https://orcid.org/0000-0001-7165-3373
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/194209
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