Related Experiment Video
Updated: Feb 7, 2026
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Selection of Protein Kinase Inhibitors Based on Tumor Tissue Kinase Activity Profiles in Patients with Refractory
Mariette Labots1, Johannes C Van der Mijn2, Henk Dekker2
1Department of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands m.labots@vumc.nl h.verheul@vumc.nl.
Lessons Learned:
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.
Background:
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.
Methods:
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.
Results:
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 response. One patient had stable disease (SD) >4 months on sunitinib; one patient had SD at 6 weeks but progressive disease (PD) at 12 weeks. The remaining patients had PD after 6 weeks of treatment.
Conclusion:
Kinase inhibition profiles of multiple PKIs can be reliably determined using fresh tumor biopsies from patients with refractory solid tumors. However, the current in vitro microarray selection approach insufficiently predicted clinical benefit of PKI treatment in these patients.
Insights
Molecular profiling of refractory solid tumors using kinase activity assays is feasible. However, this in vitro method did not reliably predict clinical benefit from selected protein kinase inhibitors (PKIs).
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Advanced solid tumors refractory to standard treatment require novel therapeutic strategies.
- Personalized medicine approaches, including protein kinase inhibitors (PKIs), offer potential for improved patient outcomes.
- Feasibility of molecular profiling for guiding PKI selection in refractory solid tumors is under investigation.
Purpose of the Study:
- To determine the feasibility and clinical benefit of selecting protein kinase inhibitors (PKIs) based on in vitro kinase activity profiling.
- To assess the utility of tyrosine kinase peptide substrate microarrays for guiding PKI selection in patients with refractory solid tumors.
Main Methods:
- Adult patients with biopsy-accessible refractory solid tumors were enrolled.
- Tumor lysates from fresh biopsies were analyzed using a tyrosine kinase peptide substrate microarray to determine the inhibitory potency of six PKIs (sunitinib, dasatinib, erlotinib, sorafenib, everolimus, lapatinib).
- The PKI with the highest in vitro activity was selected for patient treatment.
Main Results:
- Kinase inhibition profiles were successfully determined for 12 out of 13 enrolled patients.
- Eleven patients received treatment with a selected PKI, with dasatinib being the most frequently chosen agent.
- Clinical responses were limited, with one patient achieving stable disease for over four months and others progressing rapidly.
Conclusions:
- Kinase inhibition profiling using fresh tumor biopsies is a reliable method for characterizing PKI activity in refractory solid tumors.
- The current in vitro microarray-based PKI selection strategy demonstrated insufficient predictive value for clinical benefit in this patient cohort.
- Further research is needed to refine in vitro assays and improve their correlation with clinical outcomes in targeted cancer therapy.
Related Concept Videos
02:54Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
02:54Protein Kinases and Phosphatases
01:25cAMP-dependent Protein Kinase Pathways
01:26Receptor Tyrosine Kinases
02:54Molecular and Ionic Solids
Molecular Solids
Molecular crystalline solids, such as ice, sucrose (table sugar), and iodine, are solids that are composed of neutral molecules as their constituent units. These molecules are held together by weak intermolecular forces such as London dispersion forces, dipole-dipole interactions, or hydrogen bonds, which...
02:24Ribosome Profiling
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...