AXL Receptor Tyrosine Kinase as a Promising Therapeutic Target Directing Multiple Aspects of Cancer Progression and Metastasis

SIMPLE SUMMARY: Metastasis is a complex process that requires the acquisition of certain traits by cancer cells as well as the cooperation of several non-neoplastic cells that populate the stroma. Cancer-related deaths are predominantly associated with complications arising from metastases. Limiting metastasis therefore represents an important clinical challenge. The receptor tyrosine kinase AXL is required at many steps of the metastatic cascade and contributes to tumor microenvironment deregulation. In this review, we describe how AXL contributes to metastatic progression by governing various biological processes in cancer cells and in stromal cells, highlighting the potential of its inhibition. ABSTRACT: The receptor tyrosine kinase AXL is emerging as a key player in tumor progression and metastasis and its expression correlates with poor survival in a plethora of cancers. While studies have shown the benefits of AXL inhibition for the treatment of metastatic cancers, additional roles for AXL in cancer progression are still being explored. This review discusses recent advances in understanding AXL’s functions in different tumor compartments including cancer, vascular, and immune cells. AXL is required at multiple steps of the metastatic cascade where its activation in cancer cells leads to EMT, invasion, survival, proliferation and therapy resistance. AXL activation in cancer cells and various stromal cells also results in tumor microenvironment deregulation, leading to modulation of angiogenesis, fibrosis, immune response and hypoxia. A better understanding of AXL’s role in these processes could lead to new therapeutic approaches that would benefit patients suffering from metastatic diseases.