Dubermatinib -Â Model (TP-0903) - AXL Inhibitor
Dubermatinib (TP-0903) is an investigational inhibitor of AXL receptor tyrosine kinase (RTK), a protein known to be involved in acquiring resistance to chemotherapeutics, immune evasion, and developing metastatic capacity in cancer cells.9-11
Understanding the target
AXL is a founding member of the TAM (Tyro3-AXL-MER) family of RTKs. These receptors regulate tissue homeostasis and innate immune responses.15 The AXL signaling pathway has also been shown to drive and maintain a mesenchymal phenotype in cancer cells, which may increase their invasive and migratory properties, survival, and resistance to targeted therapies and immune surveillance.12-14 Targeting AXL receptor tyrosine kinase may have a therapeutic benefit in several cancer types.13,14,16
Preclinical evidence
In vitro, treatment of cancer cells with dubermatinib reverses the mesenchymal phenotype and sensitizes them to treatment with other targeted agents, eg, erlotinib/osimertinib in EGFR-mutant lung cancer and cetuximab in head and neck cancer models. In preclinical tumor models, dubermatinib restored sensitivity to erlotinib by reversing the mesenchymal phenotype driving resistance.13,14,16
Clinical development
Dubermatinib is currently being evaluated in a phase I, first-in-human trial for patients with advanced solid tumors.
