BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: AXL receptor tyrosine kinase (AXL; UFO); BRAF; MEK; microphthalmia-associated transcription factor (MITF)

February 5, 2015 8:00 AM UTC

In vitro studies suggest AXL inhibitors could help sensitize melanoma cells that express low levels of MITF to targeted therapies. In treatment-naive melanoma cell lines, low MITF expression was associated with increased resistance to BRAF and MEK inhibitors. In melanoma cells with low MITF expression, an AXL inhibitor combined with BRAF and MEK inhibitors increased cell death compared with BRAF and MEK inhibitors alone. In a panel of melanoma cell lines with acquired resistance to BRAF and MEK inhibitors, at least half showed low MITF expression levels, and these also correlated with an invasive cellular phenotype. Next steps include include testing the combination therapy strategy in patients.

Rigel Pharmaceuticals Inc. and BerGenBio A/S have the AXL inhibitor BGB324 in Phase I testing to treat various cancers. ...