[7] However, in the years since its discovery, research into AXL's expression profile and mechanism has made it an increasingly attractive target, especially for cancer therapeutics.

Although it is similar to other receptor tyrosine kinases, the Axl protein represents a unique structure of the extracellular region that juxtaposes IgL and FNIII repeats.

[6] The AXL receptor transduces signals from the extracellular matrix into the cytoplasm by binding growth factors like vitamin K-dependant protein growth-arrest-specific gene 6 (GAS6).

[15] AXL is a putative driver of diverse cellular processes that are critical for the development, growth, and spread of tumours, including proliferation, invasiveness and migration, epithelial-to-mesenchymal transition, stemness, angiogenesis, and immune modulation.

[16] Axl was first isolated in 1988 and identified as an oncogene in a screen for transforming genes in patients with a chronic myelogenous leukemia- that progressed to 'blast crisis'.

Studies have shown that AXL knockdown leads to downregulation of transcription factors required for EMT, including Slug, Twist, and Zeb1, and to increased expression of E-cadherin.

The most advanced AXL selective inhibitor is bemcentinib (BGB324 or R428), an oral small molecule currently in multiple Phase II clinical trials for NSCLC, TNBC, AML and melanoma.

Astellas Pharma is currently testing gilteritinib (ASP2215), a dual FLT3-AXL tyrosine kinase inhibitor in acute myeloid leukemia (AML).