Therapeutic Landscape of AXL Receptor Kinase in Triple-Negative Breast Cancer

Abstract Early cancer recurrence, driven by resistance to therapeutics, is a major obstacle to overcome poor survival in triple-negative breast cancer (TNBC). Recently, overexpression of AXL has been identified as one of the key molecular determinants leading to the development of acquired resistance to chemotherapy and targeted anticancer treatments. AXL overactivation drives many hallmarks of cancer progression, including cell proliferation, survival, migration, metastasis, drug resistance, and is linked to poor patient survival and disease recurrence. Mechanistically, AXL represents a signaling hub that regulates a complex signaling pathways crosstalk. Therefore, emerging data highlight the clinical significance of AXL as an attractive therapeutic target. Currently, there is no FDA approved AXL inhibitor but several AXL small molecule inhibitors and antibodies are being tested in clinical settings. In this review we outline the functions and regulation of AXL, its role in resistance to therapy, and current strategies targeting AXL with emphasis on TNBC.