Selection of Protein Kinase Inhibitors Based on Tumor Tissue Kinase Activity Profiles in Patients with Refractory Solid Malignancies: An Interventional Molecular Profiling Study

The Oncologist
Mariette LabotsHenk M W Verheul

Abstract

Clinically applicable tools are needed for treatment selection and repurposing of available protein kinase inhibitors (PKIs) in patients with advanced solid tumors refractory to standard treatment.Using a tyrosine kinase peptide substrate microarray, observed inhibitory activity in vitro could not sufficiently predict clinical benefit of treatment with the selected PKI. This exploratory molecular profiling study determined the feasibility and benefit of the selection of protein kinase inhibitors (PKIs) based on kinase activity profiling in patients with refractory solid malignancies. Adult patients with biopsy-accessible refractory solid tumors were eligible. Per patient, the inhibitory potency of sunitinib, dasatinib, erlotinib, sorafenib, everolimus, and lapatinib was determined in tumor lysates from fresh biopsies using a tyrosine kinase peptide substrate microarray. The most active PKI in this in vitro assay was selected for treatment. Thirteen patients were enrolled in the feasibility part and underwent tumor biopsy. Of 12 patients in whom kinase activity profiling was performed, 11 started treatment with a selected PKI: dasatinib in 8, sunitinib in 2, and erlotinib in 1 patient(s). Eight patients were evaluable for respon...Continue Reading

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Dec 17, 2016·Experimental & Molecular Medicine·Mariette LabotsHenk M W Verheul
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