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Preclinical and Translational Research in Thyroid Cancer
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Preclinical and Translational Research in Thyroid Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 3418

Special Issue Editors

Prof. Marialuisa Appetecchia

E-Mail Website
Guest Editor
Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy
Interests: thyroid cancer; neuroendocrine neoplasms; endocrine toxicities of antineoplastic therapy; adrenal cancer; translational cancer research
Special Issues, Collections and Topics in MDPI journals
Dr. Giulia Puliani

E-Mail Website
Co-Guest Editor
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
Interests: familial paraganglioma syndrome type 1; paraganglioma; neuroendocrine neoplasm; endocrine cancer; endocrine toxicities; thyroid; bone metabolism; adrenal cancer

Special Issue Information

Dear Colleagues,

Thyroid cancer is the most common endocrine malignancy, and its incidence is growing worldwide. Thyroid nodules include many types of cellular proliferation, from benign to intermediate and very aggressive forms. The prognosis of thyroid tumors markedly changes according to histological classification, with the more aggressive anaplastic thyroid cancers showing a five-year survival lower than 5%. Studying the pathogenesis and molecular basis of thyroid noduled and tumor development is essential, particularly also considering sex and gender differences, and possibly leading to the identification of prognostic factors. In addition, nowadays the assessment of mutations and fusions is at the base of precision medicine in oncology, and molecular characterization of the tumor needs to be considered in the selection of treatment strategy.

This Special Issue aims to provide an overview of the current knowledge regarding thyroid carcinogenesis, including risk factors, sex and/or gender differences, prognostic factors, and genetic mutations/fusions, as well as the importance of molecular profiling in thyroid cancer treatment. The submission of original basic and translational research is very encouraged, but reviews will also be considered to provide readers with an up-to-date overview of molecular aspects of thyroid cancers.

Prof. Marialuisa Appetecchia
Dr. Giulia Puliani
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • thyroid cancers
  • pathogenesis
  • molecular bases of thyroid cancer
  • precision medicine
  • gender medicine

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Published Papers (2 papers)

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Research

16 pages, 1914 KB  
Article
Inhibition of Metalloproteinases-2, -9, and -14 Suppresses Papillary Thyroid Carcinoma Cell Migration and Invasion
by Domenico Rocco, Vincenzo Marotta, Domenico Palumbo and Mario Vitale
Int. J. Mol. Sci. 2025, 26(16), 7956; https://doi.org/10.3390/ijms26167956 - 18 Aug 2025
Viewed by 280
Abstract
Papillary thyroid carcinoma (PTC), while often having a favorable prognosis, can progress to aggressive forms. Matrix metalloproteinases (MMPs) are crucial in extracellular matrix remodeling and are implicated in tumor invasion and metastasis. This study investigated MMP expression and activity in PTC and the [...] Read more.
Papillary thyroid carcinoma (PTC), while often having a favorable prognosis, can progress to aggressive forms. Matrix metalloproteinases (MMPs) are crucial in extracellular matrix remodeling and are implicated in tumor invasion and metastasis. This study investigated MMP expression and activity in PTC and the efficacy of two selective MMP inhibitors in suppressing PTC cell migration and invasion. The analysis of RNA-seq data from the TCGA-THCA dataset highlighted the overexpression of MMP-14 in PTC, a key upstream activator of several MMPs, including MMP-2 and, indirectly, MMP-9. This elevation correlated with disease status and recurrence risk. Validation in a cell model, using PTC lines (K1 and BCPAP) and non-tumoral thyroid cells (Nthy-ori 3-1), showed markedly increased MMP-14 activity in PTC lines (6-fold in K1; 11-fold in BCPAP). MMP-9 activity was also substantially elevated (386-fold in K1; 131-fold in BCPAP), along with increased MMP-2 activity. We then tested selective inhibitors. NSC405020, an MMP-14 inhibitor, reduced K1 cell migration by 56.52% and invasion by 67.3%. Gallic acid, an MMP-2 and MMP-9 inhibitor, reduced K1 cell migration to 60.3% and invasion to 33.3% relative to the controls. These findings suggest that elevated MMP activity is a hallmark of aggressive PTC, underscoring MMPs’ role in cancer progression. Targeting MMPs, particularly with agents like NSC405020 and gallic acid, presents a promising therapeutic strategy to disrupt PTC tumor progression. Full article
(This article belongs to the Special Issue Preclinical and Translational Research in Thyroid Cancer)
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Graphical abstract

20 pages, 1658 KB  
Article
Preclinical In Vitro Evaluation of Extracellular Vesicles from Human Dental Pulp Stem Cells for the Safe and Selective Modulation of Anaplastic Thyroid Carcinoma
by Anderson Lucas Alievi, Michelli Ramires Teixeira, Vitor Rodrigues da Costa, Irina Kerkis and Rodrigo Pinheiro Araldi
Int. J. Mol. Sci. 2025, 26(13), 6443; https://doi.org/10.3390/ijms26136443 - 4 Jul 2025
Viewed by 2573
Abstract
Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Precision oncology seeks personalized therapies that selectively modulate tumor behavior, which is critical for improving patient outcomes. In this study, we evaluated the therapeutic potential of human [...] Read more.
Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Precision oncology seeks personalized therapies that selectively modulate tumor behavior, which is critical for improving patient outcomes. In this study, we evaluated the therapeutic potential of human dental pulp stem cell-derived extracellular vesicles (hDPSC-EVs) in three ATC cell lines (8505C, HTH83, KTC-2). Fluorescence and confocal microscopy confirmed the efficient, time-dependent internalization of hDPSC-EVs by ATC cells, with increased fluorescence intensity over 48 h. Functional assays revealed the selective inhibition of migration and invasion in a cell line-dependent manner, without affecting cell proliferation, viability, or tumorigenic traits, indicating a non-cytotoxic, context-specific modulation of tumor behavior. After 72 h of EV treatment, targeted qPCR of 92 cancer-related genes showed the strongest response in 8505C cells (24 genes; 16 up, 8 down), moderate changes in KTC-2 (16 genes; 14 up, 2 down), and few alterations in HTH83 (6 genes; 4 up, 2 down). Across all lines, FN1 emerged as a context-dependent target, downregulated in 8505C but upregulated in the other two. No broad pathway enrichment was observed, indicating the fine-tuning of key networks rather than wholesale reprogramming. Despite variations across cell lines, hDPSC-EVs consistently demonstrated no impact on cell proliferation and no evidence of cytotoxicity or tumorigenic behavior, with no adverse outcomes. These findings provide preclinical evidence for hDPSC-EVs as a promising, safe, and targeted therapeutic platform in precision oncology, particularly for aggressive cancers, like ATC, warranting further exploration in preclinical and clinical studies. Full article
(This article belongs to the Special Issue Preclinical and Translational Research in Thyroid Cancer)
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