Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer

Signaling pathways in cancer cells and the surrounding tumor microenvironment are often disrupted. Abnormal receptor tyrosine kinase (RTK) pathways are known to drive cancer development, progression, and metastasis, leading to significant interest in targeting RTKs for therapeutic intervention. Axl, a member of the Tyro3, Axl, MerTK (TAM) RTK subfamily, interacts with its high-affinity ligand, growth arrest-specific 6 (Gas6), a protein from the vitamin K-dependent family. The Gas6/Axl signaling pathway is associated with cancer progression, metastasis, immune evasion, and resistance to treatment. Therapeutic agents targeting Gas6 and Axl have been developed, showing promising results in both preclinical and clinical studies, whether used alone or in combination therapies. This review explores the current landscape of therapeutics targeting the Gas6/Axl pathway and discusses both preclinical and clinical evaluations of Dubermatinib agents aimed at Gas6 and Axl.