Axl, a member of the TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases family, binds to its high-affinity ligand growth arrest specific 6 (Gas6), and the Gas6/Axl signaling pathway is implicated in multiple biological processes [1-3]. It plays a crucial role in cancer development, progression, metastasis, immune evasion, and drug resistance. In addition, Axl is emerging as an important regulator of neuroendocrine development and function in the hypothalamic-pituitary-gonadal axis [3].

In cancer, numerous studies have shown that Axl is involved in pro-tumorigenic processes such as cell migration, invasion, epithelial-mesenchymal transition (EMT), and stemness [4]. Reducing Axl expression can weaken cancer cells' drug resistance, indicating its potential as a target for anti-cancer drug treatment [1]. Axl also drives anti-HER2 resistance and metastasis in breast cancer through dimerization with HER2 and activation of downstream pathways, and its inhibition can restore response to HER2 blockade [2]. In NSCLC, Axl is associated with the emergence of resistance to tyrosine kinase inhibitors (TKIs) and chemotherapeutics [5].

In conclusion, Axl is a key molecule involved in both cancer-related and neuroendocrine-related biological processes. The role of Axl in promoting cancer progression and drug resistance has been well-demonstrated through various in vivo and in vitro studies. Targeting Axl, either alone or in combination with other therapies, shows promise in improving cancer treatment outcomes, especially in cancers like breast cancer and NSCLC where Axl-mediated resistance is a significant issue.