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

Jiyoung Kim^1,2, Gilyeong Nam³, You Keun Shin⁴

¹Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea.

|March 29, 2023

Summary

Targeting the AXL receptor tyrosine kinase shows promise for treating bile duct cancer. Inhibiting AXL significantly reduced tumor growth, invasion, and metastasis in preclinical models, suggesting AXL as a novel therapeutic target.

Keywords:

AVB-500 AXL bile duct cancer invasion metastatsis

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Area of Science:

Oncology
Molecular Biology
Cancer Research

Background:

Bile duct cancer (cholangiocarcinoma) has limited treatment options and a poor prognosis.
High recurrence rates necessitate the identification of novel therapeutic targets.
The receptor tyrosine kinase AXL is implicated in various cancers.

Purpose of the Study:

To investigate the role of AXL in biliary cancer progression.
To evaluate AXL as a potential therapeutic target for bile duct cancer.
To assess the efficacy of AXL inhibition using a novel agent.

Main Methods:

Analysis of AXL expression in bile duct cancer patients.
In vitro studies using bile duct cancer cell lines (SNU1196, HUCCT1) with AXL knockdown.
In vivo studies using subcutaneous and orthotopic intrahepatic tumor models.
Evaluation of AVB-500, a soluble AXL receptor, in preclinical models.

Main Results:

AXL is highly expressed in biliary cancer and correlates with poor patient outcomes, metastasis, and low survival.
Genetic knockdown of AXL inhibited tumor cell growth and invasion in vitro.
AXL inhibition via genetic means or AVB-500 delayed tumor growth in vivo.
AVB-500 effectively reduced AXL activation, tumor growth, invasion, and peritoneal dissemination.

Conclusions:

AXL receptor tyrosine kinase is a significant driver of bile duct cancer progression.
Targeting AXL represents a promising therapeutic strategy for cholangiocarcinoma.
AVB-500 demonstrates potential as a novel treatment for bile duct cancer by inhibiting AXL signaling.