Identification of Novel Therapeutic Targets in Anaplastic Thyroid Carcinoma using Functional Genomic mRNA-Profiling: Paving the way for New Avenues?

Surgery. 2016, In press.

Pascal K.C. Jonker, Gooitzen M. van Dam, Sjoukje F. Oosting, Schelto Kruijff, Rudolf S.N. Fehrmann.

Background: Currently, anaplastic thyroid carcinoma (ATC) has a very poor prognosis and there is an unmet need for new therapeutic options. Therefore, this study aims to identify upregulated genes in ATC with known drug interactions that could serve as new therapeutic targets.

Methods: Publicly available microarray expression profiles of ATC and normal thyroid tissue was collected. FGmRNA-profiling was applied, which is a recently developed method that enhances the ability to capture the downstream effects of genomic alterations on gene expression levels. Next, a comparison between FGmRNA-profiles of ATC and normal thyroid samples was performed. Significantly upregulated genes in ATC were prioritized based on: 1) association with biological pathways known to be involved in ATC carcinogenesis, 2) known interaction with anti-neoplastic drugs and 3) current drug development status in humans.

Results: 25 ATC and 80 normal thyroid samples were included for FGmRNA-profiling. Class comparison identified 389 significantly upregulated genes. Following prioritization, MTOR, MET, WEE1, PSMD1, MERTK, FGFR3, RARG and ESR2 were identified as potential therapeutic targets.

Conclusion: We prioritized eight potential therapeutic druggable targets in ATC. Ultimately, inhibition of these therapeutic targets might improve patient outcome in ATC by reducing locoregional disease and distant metastases.