Role of receptor Tyrosine Kinase AXL in cancer

Abstract

AXL is a receptor tyrosine kinase (RTK) that has emerged as a promising therapeutic target for cancer treatment. AXL plays a pivotal role in cancer progression by promoting tumor growth, migration, invasion, resistance to apoptosis, enhanced survival, and proliferation. Its overexpression in various malignancies including solid tumors and hematological cancers is strongly associated with poor prognosis. AXL signaling contributes to treatment resistance, metastatic progression, epithelial-to-mesenchymal transition (EMT), and modulation of the tumor microenvironment and immune response. Recent studies emphasize AXL’s involvement in chemotherapy resistance and highlight its potential as a therapeutic target, as evidenced by the suppression of tumor growth upon AXL inhibition in preclinical models. AXL’s relevance is particularly notable in acute myeloid leukemia, breast cancer, prostate cancer, and non-small cell lung cancer. Numerous AXL inhibitors such as small-molecule inhibitors and monoclonal antibodies have been developed, with some advancing to clinical trials offering new opportunities for targeted cancer therapies. This chapter highlights the structure and functions of AXL, mechanism for activation, role in cancer progression, and AXL-targeted therapeutic approaches. In conclusion, understanding the role of AXL in cancer progression and the engineered AXL inhibitors such as small-molecule inhibitors, monoclonal antibodies, and ligand traps holds great promise for targeted therapies for cancer treatments.