Related Experiment Video

Updated: Jul 15, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

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Differentiating Benign from Malignant Thyroid Tumors by Kinase Activity Profiling and Dabrafenib BRAF V600E Targeting

Riet Hilhorst1, Adrienne van den Berg1, Piet Boender1

  • 1PamGene International BV, 5211 HH 's-Hertogenbosch, The Netherlands.

Cancers
|September 28, 2023
PubMed

Insights

Serine/threonine kinase activity profiling accurately distinguishes benign from malignant thyroid tumors. This method also identified specific peptides for differentiating BRAF V600E-mutant papillary thyroid cancers, aiding targeted therapy selection.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Differentiated non-medullary thyroid cancer (NMTC) recurrence is linked to iodide transport loss and BRAF V600E mutations.
  • Targeted therapies for BRAF V600E mutations show variable efficacy in NMTC.
  • Next-generation sequencing (NGS) alone may not fully predict treatment response.

Purpose of the Study:

  • To assess serine/threonine kinase (STK) activity profiling for classifying benign and malignant thyroid lesions.
  • To determine if specific RAF inhibitors (dabrafenib, sorafenib, regorafenib) can differentiate BRAF V600E-mutant from non-mutant thyroid tumors.
  • To explore STK profiling as a tool for improving targeted therapy selection in recurrent thyroid cancer.

Main Methods:

  • Analysis of serine/threonine kinase activity using PamChip® peptide microarrays on 21 benign and 34 malignant frozen thyroid tumor samples.
  • Development of an STK activity classifier to differentiate tumor types.
  • Ex vivo kinase inhibition assays using dabrafenib, sorafenib, and regorafenib on BRAF V600E-mutant and non-mutant papillary thyroid cancers (PTCs).

Main Results:

  • The STK activity classifier achieved 76% accuracy in differentiating malignant (26/34) from benign (16/21) thyroid tumors.
  • PKC (theta) and PKD1 showed differential activity between benign and malignant tumors; oncocytic neoplasia and Graves' disease impacted classification.
  • Dabrafenib identified 6/92 peptides differentiating BRAF V600E-mutant from non-mutant PTCs, an effect not observed with sorafenib or regorafenib.

Conclusions:

  • STK activity profiling effectively differentiates benign from malignant thyroid tumors and generates hypotheses for differentially active kinases.
  • This approach provides a model for selecting novel kinase inhibitors based on tissue analysis.
  • Tissue-based kinase profiling may enhance the efficacy of targeted therapies for recurrent thyroid and other cancers.
Keywords:
BRAF mutationdabrafenibkinase activity profilingpeptide microarraythyroid

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