Currently, anaplastic thyroid carcinoma has a very poor prognosis and there is an unmet need for new therapeutic options. Therefore, this study aims to identify upregulated genes in anaplastic thyroid carcinoma with known drug interactions that could serve as new therapeutic targets.
Publicly available microarray expression profiles of anaplastic thyroid carcinoma and normal thyroid tissue were 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 anaplastic thyroid carcinoma and normal thyroid samples was performed. Significantly upregulated genes in ATC were prioritized based on: 1) known interaction with antineoplastic drugs, 2) current drug development status in human, and 3) association with biologic pathways known to be involved in anaplastic thyroid carcinoma carcinogenesis.
In the study, 25 anaplastic thyroid carcinoma and 80 normal thyroid samples were included for FGmRNA-profiling. Class comparison identified 301 significantly upregulated genes. Following prioritization, MTOR, MET, WEE1, PSMD1, MERTK, FGFR3, RARG, and ESR2 were identified as potential therapeutic targets.
We prioritized 8 potential therapeutic druggable targets in anaplastic thyroid carcinoma. Ultimately, inhibition of these therapeutic targets might improve patient outcome in anaplastic thyroid carcinoma by reducing locoregional disease and distant metastases.
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- Molecular pathogenesis and mechanisms of thyroid cancer.Nat Rev Cancer. 2013; 13: 184-199
- American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer.Thyroid. 2012; 22: 1104-1139
- Response and acquired resistance to everolimus in anaplastic thyroid cancer.N Engl J Med. 2014; 371: 1426-1433
- BRAF V600E inhibition in anaplastic thyroid cancer.N Engl J Med. 2013; 368: 684-685
- Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing.Hum Mol Genet. 2015; 24: 2318-2329
- Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers.J Clin Endocrinol Metab. 2008; 93: 3106-3116
- Global variation in copy number in the human genome.Nature. 2006; 444: 444-454
- Gene expression analysis identifies global gene dosage sensitivity in cancer.Nat Genet. 2015; 47: 115-125
- NCBI GEO: archive for functional genomics data sets–update.Nucleic Acids Res. 2013; 41: D991-D995
- Survival-related profile, pathways, and transcription factors in ovarian cancer.PLoS Med. 2009; 6: e24
- DGIdb: mining the druggable genome.Nat Methods. 2013; 10: 1209-1210
- Antitumor effects of proteasome inhibition in anaplastic thyroid carcinoma.J Nucl Med. 2012; 53: 1764-1771
- Carfilzomib is an effective anticancer agent in anaplastic thyroid cancer.Endocr Relat Cancer. 2015; 22: 319-329
- All-trans-retinoic acid treatment inhibits the growth of retinoic acid receptor beta messenger ribonucleic acid expressing thyroid cancer cell lines but does not reinduce the expression of thyroid-specific genes.J Clin Endocrinol Metab. 2005; 90: 2403-2411
- Anti-proliferative effect of toremifene and tamoxifen on estrogen receptor-lacking anaplastic thyroid carcinoma cell lines.Biol Pharm Bull. 1997; 20: 1257-1260
- Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer.J Clin Endocrinol Metab. 2013; 98: E811-E819
- Profile of nintedanib in the treatment of solid tumors: the evidence to date.Onco Targets Ther. 2015; 8: 3691-3701
- BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy.Cancer Res. 2008; 68: 4774-4782
- MerTK is a novel therapeutic target in gastric cancer.Oncotarget. 2015; ([Epub ahead of print])
- Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies.Leukemia. 2015; 29: 27-37
- A phase II study of AT9283, an aurora kinase inhibitor, in patients with relapsed or refractory multiple myeloma: NCIC clinical trials group IND.191.Leuk Lymphoma. 2015; 15: 1-4
- Phase I study of single-agent AZD1775 (MK-1775), a WEE1 kinase inhibitor, in patients with refractory solid tumors.J Clin Oncol. 2015; 33: 3409-3415
- The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma.Ann Surg Oncol. 2002; 9: 57-64
Published online: November 16, 2016
Accepted: June 18, 2016
Supported by the Bas Mulder award of Alpe d’HuZes/Dutch Cancer Society (RUG 2013–5960) and a Mandema Stipendium to R.S.N. Fehrmann.
© 2016 Elsevier Inc. All rights reserved.