Table 1 Representative agents of TAM-targeted therapy
From: Immuno-oncology: are TAM receptors in glioblastoma friends or foes?
| Agents | Action features | Mechanisms or effects on GBM | References |
|---|---|---|---|
| BGB324 | Small molecule inhibitor targeting Axl | Motivate tumor cell apoptosis, suppress GBM proliferation, migration, invasion and survival | [122, 145] |
| BMS-777607 | Increase intratumoral apoptosis, impair neovascularization, proliferation and invasion | [28, 146] | |
| N-butylidenephthalide (BP) | A novel small molecule targeting Axl | Increase gliadel wafer local drug concentration and extend its diffusion distance. Downregulate the expression of Axl and reduce the migratory and invasive capabilities of GBM cells | [137] |
| TP‐0903 | Anti‐Axl antibodies | Intensify sensitivity to TMZ and significantly reverse TMZ resistance in GBM. Promote the proportion of apoptosis and enhance the cytotoxicity of TMZ, thereby dramatically decreasing tumor growth | [144] |
| AXL-DN | A dominant-negative mutant receptor against Axl | Suppress diffuse-invasive GBM growth and prolong survival | [138] |
| UNC2025 | Orally bioavailable small molecule inhibitor of Mer | Reduce clonal expansion, colony-forming potential, and neurosphere diameter in GBM cells. Possess strong penetration of brain | [136, 140] |
| Small interfering RNA | Nucleotide aptamer binding to Mer | Cause morphological change of GBM cells, decrease GBM migration and resistance to chemotherapy | [142] |
| Small interfering RNA | Inducible shRNA-mediated knockdown of Mer and Axl | Increase apoptosis and autophagy, decrease nonadherent colony formation, enhance chemosensitivity | [115] |
| UNC1062 | Pyrazolopyrimidine sulfonamides, small molecule inhibitor against Mer | Inhibit Mer phosphorylation and colony formation, activate anti-tumor immunity | [153] |
| Foretinib | Multi kinase inhibitor, primarily targeted at c-Met and VEGFR2/KDR; meanwhile, inhibition of Mer and, to a lesser extent, Axl and Tyro3 | Inhibit the activation of TAM family receptors and the oncogenic signaling pathways. Decrease cellular survival, migration and invasion of glioma cells | [139] |