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Thyroid Cancer Metastases (Biological and Clinical Aspects)

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 13353

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Special Issue Editors

Dr. Vasyl Vasko

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Guest Editor

Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
Interests: thyroid cancer; metastases; oncogenes; cell signaling; liquid biopsy

Dr. Kirk Jensen

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Guest Editor

Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Interests: thyroid cancer; mitochondria; oncogenes; mutations/fusions; liquid biopsy; digital PCR

Special Issue Information

Dear Colleagues,

Thyroid cancer progression is a complex, multistep process, and epithelial–mesenchymal transition (EMT) is currently considered to be a critical mechanism underlying thyroid cancer cells invasion and development of metastases. EMT is orchestrated by a network of transcription factors, growth factors, signaling cascades, and epigenetic modulators. Loco-regional metastases are often present in patients with thyroid cancers. Importantly, up to 20% of thyroid cancer patients develop distant metastases, and one-third become radioiodine refractory. Available targeted therapies increase progression-free survival but are associated with toxicities. In this Special Issue, we encourage submission of manuscripts focusing on molecular mechanisms of thyroid cancer metastases, as well as clinical research providing novel findings in the diagnosis and treatment of metastatic thyroid cancer.

Dr. Vasyl Vasko
Dr. Kirk Jensen
Guest Editors

Manuscript Submission Information

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Keywords

epithelial-to-mesenchymal transition
thyroid cancer metastases
recurrences
targeted therapy

Published Papers (3 papers)

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Research

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14 pages, 3459 KiB

Open AccessArticle

Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma

by Chen-Kai Chou, Shun-Yu Chi, Fong-Fu Chou, Shun-Chen Huang, Jia-He Wang, Chueh-Chen Chen and Hong-Yo Kang

Cancers 2020, 12(5), 1109; https://doi.org/10.3390/cancers12051109 - 29 Apr 2020

Cited by 11 | Viewed by 2491

Abstract

Male gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (AR) gene expression on the clinical features and progression of PTC. The levels of AR mRNA and protein in frozen, formalin-fixed, paraffin-embedded tissue samples from PTC and adjacent normal thyroid tissue were assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining, respectively, and the relationships between AR expression and clinical features were analyzed. The thyroid cancer cell lines, BCPAP and TPC-1, were used to evaluate the effects of AR on the regulation of cell migration, and key epithelial–mesenchymal transition (EMT) markers. AR mRNA expression was significantly higher in normal thyroid tissue from men than women. The sex difference in AR mRNA expression diminished during PTC tumorigenesis, as AR mRNA expression levels were lower in PTC than normal thyroid tissues from both men and women. AR mRNA expression was significantly decreased in PTC patients with higher risk and in those with extrathyroidal extension. Overexpression of AR in BCPAP cells decreased cell migration and repressed the EMT process by down-regulating mRNA expression of N-cadherin, Snail1, Snail2, Vimentin, and TWIST1 and up-regulating E-cadherin gene expression. These results suggest that suppression of the androgen–AR axis may lead to aggressive tumor behavior in patients with PTC. Full article

(This article belongs to the Special Issue Thyroid Cancer Metastases (Biological and Clinical Aspects))

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Review

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14 pages, 1506 KiB

Open AccessReview

Uncommon Site of Metastasis and Prolonged Survival in Patients with Anaplastic Thyroid Carcinoma: A Systematic Review of the Literature

by Aurora Mirabile, Matteo Biafora, Leone Giordano, Gianluigi Arrigoni, Maria Giulia Cangi, Italo Dell’Oca, Francesca Lira Luce, Davide Di Santo, Andrea Galli, Michele Tulli, Renata Mellone, Davide Valsecchi, Vanesa Gregorc and Mario Bussi

Cancers 2020, 12(9), 2585; https://doi.org/10.3390/cancers12092585 - 10 Sep 2020

Cited by 6 | Viewed by 2065

Abstract

Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization. Full article

(This article belongs to the Special Issue Thyroid Cancer Metastases (Biological and Clinical Aspects))

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37 pages, 3091 KiB

Open AccessReview

Novel Targeted Therapies for Metastatic Thyroid Cancer—A Comprehensive Review

by Mohammad Al-Jundi, Shilpa Thakur, Sriram Gubbi and Joanna Klubo-Gwiezdzinska

Cancers 2020, 12(8), 2104; https://doi.org/10.3390/cancers12082104 - 29 Jul 2020

Cited by 45 | Viewed by 8407

Abstract

The knowledge on thyroid cancer biology has grown over the past decade. Thus, diagnostic and therapeutic strategies to manage thyroid cancer are rapidly evolving. With new insights into tumor biology and cancer genetics, several novel therapies have been approved for the treatment of thyroid cancer. Tyrosine kinase inhibitors (TKIs), such as lenvatinib and sorafenib, have been successfully utilized for the treatment of radioactive iodine (RAI)-refractory metastatic differentiated thyroid cancer (DTC). In addition, pretreatment with mitogen-activated protein kinase (MAPK) inhibitors (trametinib and selumetinib) has been shown to restore RAI avidity in previously RAI-refractory DTCs. Local therapies, such as external beam radiation and radiofrequency/ethanol ablation, have also been employed for treatment of DTC. Vandetanib and cabozantinib are the two TKIs currently approved by the Food and Drug Administration (FDA) for the treatment of medullary thyroid cancer (MTC). Other novel therapies, such as peptide receptor radionuclide therapy and carcinoembryonic antigen (CEA) vaccine, have also been utilized in treating MTC. Ongoing trials on selective rearranged-during-transfection (RET) protooncogene inhibitors, such as LOXO-292 and BLU-667, have demonstrated promising results in the treatment of metastatic MTC resistant to non-selective TKIs. The FDA-approved BRAF/MEK inhibitor combination of dabrafenib and trametinib has revolutionized treatment of BRAF^V600E mutation positive anaplastic thyroid cancer. Several other emerging classes of medications, such as gene fusion inhibitors and immune checkpoint inhibitors, are being actively investigated in several clinical trials. In this review, we describe the molecular landscape of thyroid cancer and novel targeted therapies and treatment combinations available for the treatment of metastatic thyroid cancer. Full article

(This article belongs to the Special Issue Thyroid Cancer Metastases (Biological and Clinical Aspects))

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