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An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 22675

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Special Issue Editor

Dr. Zhilong Ai

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Guest Editor

Department of Surgery (Thyroid & Breast), Zhongshan Hospital, Fudan University, Shanghai, China
Interests: thyroid cancer; cancer treatment; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thyroid cancer (TC) ranked 9th in terms of malignant tumor incidence worldwide in 2020 and 5th among females, thereby establishing itself as a significant threat to population health. Although TC generally exhibits a better prognosis compared to other cancers, poorly differentiated thyroid cancer, a subtype of TC, displays the shortest average survival time. The precise cause of TC's high incidence remains unclear, particularly the molecular mechanisms underlying its development. Consequently, the primary approaches for treating TC involve surgery, often supplemented by 131I therapy, radiotherapy, endocrine therapy, and biomarker-targeted therapy. Unfortunately, these treatments, except for targeted biological therapies, often result in irreversible harm to patients, such as thyroidectomy or radiation injuries. While targeted therapy can be expensive, and current TC biomarkers remain limited, their effects are still being explored. Additionally, aside from surgical resection, alternative treatment methods remain subject to ongoing controversy.

We are pleased to invite you to publish papers spanning basic, translational, and other aspects of thyroid cancer. Original contributions should encompass a broad spectrum of topics within the field, spanning from molecular and cellular biology to immunology, biochemistry, physiology, pathology, and the treatment of both pediatric and adult thyroid cancer. A special emphasis will be placed on thyroid cancer therapy and the molecular mechanisms.

This Special Issue aims to original research articles and comprehensive reviews related to thyroid cancer. The contents may include, but are not limited to, the following subtopics:

Molecular regulations in thyroid cancer.
Cancer treatment via immunotherapeutic, biochemical, and other approaches.
Mechanisms underlying the occurrence, development, and deterioration of thyroid cancer.
Novel biomarkers for diagnosing, treating, and predicting prognosis in thyroid cancer.
Thyroid cancer research with new methods and technologies, including multi-omics, single cell sequencing, etc.

We look forward to receiving your contributions.

Dr. Zhilong Ai
Guest Editor

Manuscript Submission Information

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Keywords

thyroid cancer
mechanisms
treatments
biomarkers
precision medicine
infiltration
metastasis

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Published Papers (9 papers)

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Research

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11 pages, 4286 KiB

Open AccessArticle

Management of Giant Thyroid Tumors in Patients with Multiple Comorbidities in a Tertiary Head and Neck Surgery Center

by Daniela Vrinceanu, Mihai Dumitru, Andreea Marinescu, Crenguta Serboiu, Gabriela Musat, Mihai Radulescu, Matei Popa-Cherecheanu, Catalina Ciornei and Felicia Manole

Biomedicines 2024, 12(10), 2204; https://doi.org/10.3390/biomedicines12102204 - 27 Sep 2024

Cited by 6 | Viewed by 1109

Abstract

Background/Objectives: The thyroid gland can represent the seat of development for giant tumors exceeding 10 cm in diameter. A retrospective analysis on 21 cases of giant thyroid tumors with comorbidities, operated in the ENT Department of the Bucharest University Emergency Hospital has been conducted. Methods: Giant benign tumors accounted for 28.57% of the cases studied and reached gigantic volumes in an average time interval of 3 years, with an average resection piece weight of 318 g. Malignant tumors accounted for 71.43%, with an average duration of evolution of 7 years, with an average resection piece weight of 581 g. Results: Dysphagia was present in all patients, dyspnea in 47.61% and dysphonia in 38.09% of cases. Total thyroidectomy is the gold standard in giant thyroid tumors, associated with radical neck dissection, extended to groups VI and VII in malignant tumors. In 10 of 11 cases of giant malignant thyroid tumors (90.90%), without anaplastic thyroid carcinoma, the survival at 5 years after multimodal oncologic treatment was favorable. Anticoagulant treatment increased the risk of postoperative reversible recurrent laryngeal nerve lesion. Conclusions: The management of giant thyroid tumors in patients with multiple comorbidities needs a multidisciplinary team including endocrinologist, radiologist, anesthesiologist, pathologist, ENT surgeon, thoracic surgeon, oncologist and radiotherapist. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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12 pages, 452 KiB

Open AccessArticle

The Role of Body Mass Index (BMI) in Differentiated Thyroid Cancer: A Potential Prognostic Factor?

by Chiara Mele, Lucrezia De Marchi, Giulia Marsan, Marco Zavattaro, Maria Grazia Mauri, Paolo Aluffi Valletti, Gianluca Aimaretti and Paolo Marzullo

Biomedicines 2024, 12(9), 1962; https://doi.org/10.3390/biomedicines12091962 - 29 Aug 2024

Viewed by 1112

Abstract

Obesity has been recognized as a potential risk factor for the carcinogenesis of differentiated thyroid cancer (DTC). The aim of this observational study was to investigate the prognostic role of BMI in influencing DTC histopathological aggressiveness and the risk of tumor relapse. We enrolled 257 patients with DTC, consecutively admitted to our Institution between January 2016 and December 2023. The following variables were collected: demographic, anthropometric and clinical parameters, risk factors for DTC, surgical and radioiodine therapy, histopathological features of DTC, and biochemical markers of disease. Tumor recurrence was assessed during short-, medium- and long-term follow-up. According to BMI tertiles (e.g; I: BMI < 23.3 kg/m²; II: 23.3 ≤ BMI < 27.1 kg/m²; III: BMI ≥ 27.1 kg/m²), the clinical and histopathological characteristics did not differ between groups. The multinomial logistic regression analysis showed that BMI was not associated with clinical and histopathological aggressiveness of DTC, independently from sex, age, and risk factors for DTC onset. Moreover, BMI did not constitute a predictor of tumor recurrence during follow-up. In conclusion, BMI does not represent a predictor of clinical and histopathological aggressiveness of DTC. Since it is not a reliable marker of adiposity, BMI cannot be considered alone in evaluating the potential association between obesity and DTC prognosis. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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13 pages, 1298 KiB

Open AccessArticle

The Effect of Radioiodine Therapy on the Prognosis of Differentiated Thyroid Cancer with Lung Metastases

by Shenghong Zhang, Mengqin Zhu, Han Zhang, Hanhui Liu, Xin Fan, Jiajia Zhang and Fei Yu

Biomedicines 2024, 12(3), 532; https://doi.org/10.3390/biomedicines12030532 - 27 Feb 2024

Cited by 3 | Viewed by 2513

Abstract

Lung metastasis substantially influences the survival of thyroid cancer (TC) patients. This study sought to investigate factors impacting the survival of differentiated thyroid cancer patients with lung metastases (DTC–LM) undergoing radioiodine therapy (RAI) after thyroid surgery. The retrospective study encompassed 609 TC patients with lung metastases. Survival outcomes—specifically, overall survival (OS) and thyroid cancer-specific survival (TCSS)—were examined through both univariate and multivariate Cox regression analyses. Radioiodine therapy (RAI)’s impact on DTC–LM patient survival was further assessed with the Kaplan–Meier survival curve. Of the 609 TC patients with lung metastases, 434 (71.3%) were found to have undergone thyroid surgery after a median follow-up of 59 months. Anaplastic thyroid cancer (ATC), stage IV, and lung metastases associated with other metastases were identified as risk factors for OS and TCSS in TCLM patients. RAI therapy significantly enhances survival in DTC–LM patients followed by primary site surgery under the age of 55, PTC patients, and those with single organ metastases at lung. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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12 pages, 1821 KiB

Open AccessArticle

Association of BRAF V600E Mutant Allele Proportion with the Dissemination Stage of Papillary Thyroid Cancer

by Ivan Blazekovic, Ivan Samija, Josipa Perisa, Koraljka Gall Troselj, Tihana Regovic Dzombeta, Petra Radulovic, Matija Romic, Roko Granic, Ines Sisko Markos, Ana Frobe, Zvonko Kusic and Tomislav Jukic

Biomedicines 2024, 12(3), 477; https://doi.org/10.3390/biomedicines12030477 - 21 Feb 2024

Cited by 1 | Viewed by 2074

Abstract

The early identification of aggressive forms of cancer is of high importance in treating papillary thyroid cancer (PTC). Disease dissemination is a major factor influencing patient survival. Mutation status of BRAF oncogene, BRAF V600E, is proposed to be an indicator of disease recurrence; however, its influence on PTC dissemination has not been deciphered. This study aimed to explore the association of the frequency of BRAF V600E alleles in PTC with disease dissemination. In this study, 173 PTC samples were analyzed, measuring the proportion of BRAF V600E alleles by qPCR, which was then normalized against the proportion of tumor cells. Semiquantitative analysis of BRAF V600E mutant protein was performed by immunohistochemistry. The BRAF V600E mutation was present in 60% of samples, while the normalized frequency of mutated BRAF alleles ranged from 1.55% to 92.06%. There was no significant association between the presence and/or proportion of the BRAF V600E mutation with the degree of PTC dissemination. However, the presence of the BRAF mutation was significantly linked with angioinvasion. This study’s results suggest that there is a heterogeneous distribution of the BRAF mutation and the presence of oligoclonal forms of PTC. It is likely that the BRAF mutation alone does not significantly contribute to PTC aggressiveness. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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13 pages, 643 KiB

Open AccessArticle

Minimal Extrathyroid Extension (mETE) as the Only Risk Factor in Patients with Papillary Thyroid Carcinoma (PC): Its Clinical Impact on Recurrence and Outcome during Long-Term Follow-Up

by Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Sonia Vargiu, Angela Spanu and Giuseppe Madeddu

Biomedicines 2024, 12(2), 350; https://doi.org/10.3390/biomedicines12020350 - 2 Feb 2024

Cited by 2 | Viewed by 1899

Abstract

Minimal extrathyroid extension (mETE) effect on papillary thyroid carcinoma (PC) prognosis is still debated even more so now that this factor has been removed in the 8th AJCC Edition, supporting the hypothesis that mETE is not associated with aggressive tumors. We retrospectively enrolled 91 PC patients (Group 1) submitted to total thyroidectomy and radioiodine ablation. At the time of the primary tumor surgery, mETE was ascertained in all patients with no other risk factors, such as multifocality, vascular invasion, neck and distant metastases, and aggressive histological variants. As controls, 205 consecutive matched PC patients (Group 2) without mETE and the aforementioned risk factors were enrolled. During the follow-up (average 8 years), 16/91 (17.58%) Group 1 patients and 15/205 (7.32%) Group 2 patients developed metastases (p = 0.0078). Cox regression analysis showed an increased risk of metastases in patients with mETE (HR: 2.58 (95% CI 1.28–5.22) p = 0.008). Disease-free survival (DFS) was significantly lower in patients with mETE than in controls (p = 0.0059). The present study seems to demonstrate that mETE can be associated with an aggressive PC and can be considered, even alone without other risk factors, an independent factor of unfavorable DFS. Thus, by excluding mETE in the 8th AJCC Edition, patient care and management could be compromised. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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17 pages, 1689 KiB

Open AccessReview

The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy

by Bahejuan Jiaerken, Wei Liu, Jiaojiao Zheng, Weifeng Qu, Qiao Wu and Zhilong Ai

Biomedicines 2024, 12(10), 2408; https://doi.org/10.3390/biomedicines12102408 - 21 Oct 2024

Cited by 1 | Viewed by 1744

Abstract

(1) Background: Small ubiquitin-like modifiers (SUMOs) are pivotal in post-translational modifications, influencing various cellular processes, such as protein localization, stability, and genome integrity. (2) Methods: This review explores the SUMO family, including its isoforms and catalytic cycle, highlighting their significance in regulating key biological functions in thyroid cancer. We discuss the multifaceted roles of SUMOylation in DNA repair mechanisms, protein stability, and the modulation of receptor activities, particularly in the context of thyroid cancer. (3) Results: The aberrant SUMOylation machinery contributes to tumorigenesis through altered gene expression and immune evasion mechanisms. Furthermore, we examine the therapeutic potential of targeting SUMOylation pathways in thyroid cancer treatment, emphasizing the need for further research to develop effective SUMOylation inhibitors. (4) Conclusions: By understanding the intricate roles of SUMOylation in cancer biology, we can pave the way for innovative therapeutic strategies to improve outcomes for patients with advanced tumors. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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21 pages, 1494 KiB

Open AccessReview

Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer

by Kazumasa Sekihara, Hidetomo Himuro, Soji Toda, Nao Saito, Ryoichi Hirayama, Nobuyasu Suganuma, Tetsuro Sasada and Daisuke Hoshino

Biomedicines 2024, 12(6), 1286; https://doi.org/10.3390/biomedicines12061286 - 10 Jun 2024

Cited by 2 | Viewed by 2589

Abstract

Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy characterized by advanced disease at diagnosis and a poor prognosis. Despite multimodal therapeutic approaches that include surgery, radiotherapy, and chemotherapy, an optimal treatment strategy remains elusive. Current developments in targeted therapies and immunotherapy offer promising avenues for improved outcomes, particularly for BRAF-mutant patients. However, challenges remain regarding overcoming drug resistance and developing effective treatments for BRAF-wild-type tumors. This comprehensive review examines the clinical and biological features of ATC, outlines the current standards of care, and discusses recent developments with a focus on the evolving role of radiotherapy. Moreover, it emphasizes the necessity of a multidisciplinary approach and highlights the urgent need for further research to better understand ATC pathogenesis and identify new therapeutic targets. Collaborative efforts, including large-scale clinical trials, are essential for translating these findings into improved patient outcomes. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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12 pages, 3546 KiB

Open AccessReview

Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification

by Tomohiro Chiba

Biomedicines 2024, 12(4), 712; https://doi.org/10.3390/biomedicines12040712 - 22 Mar 2024

Cited by 8 | Viewed by 7422

Abstract

In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th), was published. Large-scale genomic analyses such as The Cancer Genome Atlas (TCGA) have revealed the importance of understanding the molecular genetics of thyroid tumors. Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on the cell of origin of tumors and their clinical risk. This paper outlines the following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDNs) highlight the role of mutations in the MAP kinase pathway, including RET, RAS, and BRAF, as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: RAS-like tumors (RLTs) and BRAF p.V600E-like tumors (BLTs), respectively. 2. The framework for benign lesions has been revised. The WHO 5th introduces a new category: “developmental abnormalities”. Benign FDNs comprise “thyroid follicular nodular disease”, follicular thyroid adenoma (FTA), FTA with papillary architecture, and oncocytic adenoma (OA). “Hürthle cell adenoma/carcinoma” is renamed oncocytic adenoma/carcinoma of the thyroid (OA/OCA), which can be distinguished from FTA/FTC by its unique genetic background. 3. Low-risk tumors include NIFTP, TT-UMP, and HTT, and they have an extremely low malignant potential or an uncertain malignant potential. 4. PTC histological variants are reclassified as “subtypes” in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to their shared genetic and prognostic features. 7. Other miscellaneous tumors are categorized as salivary-gland-type carcinomas of the thyroid, thyroid tumors of uncertain histogenesis, thymic tumors within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on both genetic abnormalities and histomorphology. This approach aids in achieving accurate pathological diagnosis and facilitates the early selection of appropriate treatment options, including molecular targeted therapies. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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Other

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13 pages, 1964 KiB

Open AccessCase Report

Treatment Outcomes and Toxicities of Multiple Tyrosin Kinase Inhibitors for Metastatic Medullary Thyroid Cancer: A Case Series

by Marilda Mormando, Rosa Lauretta, Giulia Puliani, Marta Bianchini, Maria Elena Spoltore and Marialuisa Appetecchia

Biomedicines 2024, 12(12), 2923; https://doi.org/10.3390/biomedicines12122923 - 23 Dec 2024

Viewed by 841

Abstract

Background: The current possible treatments of advanced medullary carcinoma (MTC) include different drugs belonging to the class of tyrosine kinase inhibitors (TKIs): vandetanib, cabozantinb, and selpercatinib. Although the effects of these TKIs have been well described in clinical trials, the real-practice evidence of the effectiveness and safety of these treatment is scant. This real-world case series aims to describe a niche of patients with advanced MTC treated with more than one TKI by focusing on treatment responses and any reported adverse events (AEs) and to provide additional insight on the individualized approach to the management of metastatic MTC. Methods: Five patients with a diagnosis of metastastic MTC, treated with at least two different molecules of TKIs, were retrospectively selected. Results: Three patients obtained a partial response (one with cabozantinb, one with selpercatinib, and one with vandetanib), and two patients obtained disease stability (both of them treated with all three TKIs, the first two lines discontinued for AEs). The AE profile agreed with the known clinical trials AEs except for non-neoplastic ascites related to selpercatinib and lung cavitations of non-neoplastic tissue related to cabozantinb. The latter was an AE never described so far in patients receiving TKIs. Conclusions: The best management of MTC relies on an individualized approach, keeping in mind and dealing with the potential toxicity in order to minimize the treatment withdrawal. Full article

(This article belongs to the Special Issue An Update on Mechanisms and Treatments for Thyroid Cancer in Current Oncology)

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