Axl, a member of the TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases family (RTKs), binds to its high-affinity ligand growth arrest specific 6 (Gas6), and the Gas6/Axl signaling pathway is involved in multiple biological processes [1,2]. Axl is associated with normal neuroendocrine development and function, impacting the hypothalamic-pituitary-gonadal axis, and is also implicated in various reproductive diseases [4]. In the context of cancer, it has emerged as a crucial factor [1-4,6-10].

In cancer, Axl is linked to tumorigenic processes such as cell migration, invasion, epithelial-mesenchymal transition (EMT), stemness, metastasis, and drug resistance [1,2,4,6-10]. For example, in breast cancer, preclinical studies show Axl drives anti-HER2 resistance and metastasis through dimerization with HER2 [3]. In NSCLC, Axl is associated with resistance to tyrosine kinase inhibitors and chemotherapeutics [5]. Additionally, the Gas6/Axl signaling pathway can trigger actin remodeling, promoting cancer-cell invasion [6].

In conclusion, Axl is a significant receptor tyrosine kinase involved in both normal physiological processes like neuroendocrine function and pathological conditions, especially cancer. Its role in cancer progression and drug resistance, as revealed through various in-vitro and pre-clinical models, highlights its potential as a therapeutic target in oncology [1-4,6-10].

References:

1. Tang, Yaoxiang, Zang, Hongjing, Wen, Qiuyuan, Fan, Songqing. 2023. AXL in cancer: a modulator of drug resistance and therapeutic target. In Journal of experimental & clinical cancer research : CR, 42, 148. doi:10.1186/s13046-023-02726-w. https://pubmed.ncbi.nlm.nih.gov/37328828/

2. Tanaka, Mai, Siemann, Dietmar W. 2021. Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer. In International journal of molecular sciences, 22, . doi:10.3390/ijms22189953. https://pubmed.ncbi.nlm.nih.gov/34576116/

3. Adam-Artigues, Anna, Arenas, Enrique J, Arribas, Joaquín, Prat, Aleix, Cejalvo, Juan Miguel. 2023. AXL - a new player in resistance to HER2 blockade. In Cancer treatment reviews, 121, 102639. doi:10.1016/j.ctrv.2023.102639. https://pubmed.ncbi.nlm.nih.gov/37864955/

4. Mohammadzadeh, Pardis, Amberg, Gregory C. 2023. AXL/Gas6 signaling mechanisms in the hypothalamic-pituitary-gonadal axis. In Frontiers in endocrinology, 14, 1212104. doi:10.3389/fendo.2023.1212104. https://pubmed.ncbi.nlm.nih.gov/37396176/

5. Zaman, Aubhishek, Bivona, Trever G. 2021. Targeting AXL in NSCLC. In Lung Cancer (Auckland, N.Z.), 12, 67-79. doi:10.2147/LCTT.S305484. https://pubmed.ncbi.nlm.nih.gov/34408519/

6. Zdżalik-Bielecka, Daria, Poświata, Agata, Kozik, Kamila, Stenmark, Harald, Miączyńska, Marta. . The GAS6-AXL signaling pathway triggers actin remodeling that drives membrane ruffling, macropinocytosis, and cancer-cell invasion. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2024596118. https://pubmed.ncbi.nlm.nih.gov/34244439/