Document Type
Article
Publication Date
2-10-2025
Abstract
AXL, a member of the TAM receptor family, has emerged as a potential target for advanced-stage human malignancies. It is frequently overexpressed in different cancers and plays a significant role in various tumor-promoting pathways, including cancer cell proliferation, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, stemness, DNA damage response, acquired therapeutic resistance, immunosuppression, and inflammatory responses. Beyond oncology, AXL also facilitates viral infections, including SARS-CoV-2 and Zika highlighting its importance in both cancer and virology. In preclinical models, small-molecule kinase inhibitors targeting AXL have shown promising anti-tumorigenic potential. This review primarily focuses on the induction, regulation and biological functions of AXL in mediating these tumor-promoting pathways. We discuss a range of therapeutic strategies, including recently developed small-molecule tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and antibody-drug conjugates (ADCs), anti-AXL-CAR, and combination therapies. These interventions are being examined in both preclinical and clinical studies, offering the potential for improved drug sensitivity and therapeutic efficacy. We further discuss the mechanisms of acquired therapeutic resistance, particularly the crosstalk between AXL and other critical receptor tyrosine kinases (RTKs) such as c-MET, EGFR, HER2/HER3, VEGFR, PDGFR, and FLT3. Finally, we highlight key research areas that require further exploration to enhance AXL-mediated therapeutic approaches for improved clinical outcomes.
Recommended Citation
Yadav, Monika; Sharma, Akansha; Patne, Ketki; Tabasum, Saba; Suryavanshi, Jyoti; Rawat, Laxminarayan; Machaalani, Marc; Eid, Marc; Singh, Rana; Choueiri, Toni; Pal, Soumitro; and Sabarwal, Akash, "AXL Signaling in Cancer: From Molecular Insights to Targeted Therapies" (2025). Department of Microbiology and Immunology Faculty Papers. Paper 193.
https://jdc.jefferson.edu/mifp/193
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
39924521
Language
English
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Chemical and Pharmacologic Phenomena Commons, Chemicals and Drugs Commons, Microbiology Commons
Comments
This article is the author's final published version in Signal Transduction and Targeted Therapy, Volume 10, Issue 1, 2025, Article number 37.
The published version is available at https://doi.org/10.1038/s41392-024-02121-7.
Copyright © The Author(s) 2025