A New Assay Detects MET Phosphorylation in Tumor Biopsies — A Validated Tool to Measure the Activation of a Protein Implicated in Cancer

MET (hepatocyte growth factor receptor) is a trans-membrane, tyrosine kinase receptor whose aberrant signaling is implicated in cancer growth, progression, and metastasis.  Currently, many drugs are in development that target MET kinase signaling; however, until now, no assay has been available to effectively measure MET pharmacodynamics directly in core biopsies of tumors, which is a critical capability for proof of mechanism studies to confirm intended drug action in patients. Researchers from NCI’s Division of Cancer Treatment and Diagnosis (DCTD) recently developed and validated an immunoassay that measures MET protein and phosphorylation levels at key amino acid residues that trigger MET signaling and must be controlled by drug treatment. The authors also determined through biopsy handling studies that phosphorylated MET in core needle biopsies is highly unstable and can only be preserved for analysis if biopsy specimens are flash frozen within 2 minutes of collection. This new immunoassay will be a powerful clinical tool because it will allow clinicians to measure the effectiveness of MET kinase inhibitors directly in the tumor and evaluate if drug therapy achieves the level of inhibition of MET signaling associated with tumor regression in laboratory models.

Reference

Srivastava AK, Hollingshead MG, Weiner J, Navas T, Evrard YA, Khin S, Ji J, Zhang Y, Borgel S, Pfister TD, Kinders RJ, Bottaro DP, Linehan WM, Tomaszewski JE, Doroshow JH, Parchment RE. Pharmacodynamic Response of the MET/HGF-Receptor to Small Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays. Clin Cancer Res. 2016 Jul 15;22(14):3683-94.