scholarly journals A New Aurora in Anaplastic Thyroid Cancer Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Enke Baldini ◽  
Massimino D’Armiento ◽  
Salvatore Ulisse
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Human Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Malignant Cell ◽  
Thyroid Tumor ◽  
Antitumor Effects ◽  
Aurora Kinases ◽  
Mitotic Kinases ◽  
Human Cancers

Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation.

scholarly journals MicroRNA Deregulation in Anaplastic Thyroid Cancer Biology

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Cesar Seigi Fuziwara ◽  
Edna Teruko Kimura
Keyword(s):  
Thyroid Cancer ◽  
Tumor Suppressor ◽  
Cancer Progression ◽  
Cell Biology ◽  
Cancer Biology ◽  
Anaplastic Thyroid Cancer ◽  
Genetic Alterations ◽  
Thyroid Tumor ◽  
Mesenchymal Transition ◽  
Promising Therapeutic Approach

Anaplastic thyroid cancer (ATC) is among the most lethal types of cancers, characterized as a fast-growing and highly invasive thyroid tumor that is unresponsive to surgery and radioiodine, blunting therapeutic efficacy. Classically, genetic alterations in tumor suppressorTP53are frequent, and cumulative alterations in different signaling pathways, such as MAPK and PI3K, are detected in ATC. Recently, deregulation in microRNAs (miRNAs), a class of small endogenous RNAs that regulate protein expression, has been implicated in tumorigenesis and cancer progression. Deregulation of miRNA expression is detected in thyroid cancer. Upregulation of miRNAs, such asmiR-146b,miR-221, andmiR-222, is observed in ATC and also in differentiated thyroid cancer (papillary and follicular), indicating that these miRNAs’ overexpression is essential in maintaining tumorigenesis. However, specific miRNAs are downregulated in ATC, such as those of themiR-200andmiR-30families, which are important negative regulators of cell migration, invasion, and epithelial-to-mesenchymal transition (EMT), processes that are overactivated in ATC. Therefore, molecular interference to restore the expression of tumor suppressor miRNAs, or to blunt overexpressed oncogenic miRNAs, is a promising therapeutic approach to ameliorate the treatment of ATC. In this review, we will explore the importance of miRNA deregulation for ATC cell biology.

scholarly journals Strategies for manipulating the p53 pathway in the treatment of human cancer

2000 ◽  
Vol 352 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Ted R. HUPP ◽  
David P. LANE ◽  
Kathryn L. BALL
Keyword(s):  
Cancer Progression ◽  
Human Cancer ◽  
P53 Protein ◽  
Metastatic Potential ◽  
Biochemical Properties ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
P53 Pathway ◽  
Environmental Pressures ◽  
Human Cancers

Human cancer progression is driven in part by the mutation of oncogenes and tumour-suppressor genes which, under selective environmental pressures, give rise to evolving populations of biochemically altered cells with enhanced tumorigenic and metastatic potential. Given that human cancers are biologically and pathologically quite distinct, it has been quite surprising that a common event, perturbation of the p53 pathway, occurs in most if not all types of human cancers. The central role of p53 as a tumour-suppressor protein has fuelled interest in defining its mechanism of function and regulation, determining how its inactivation facilitates cancer progression, and exploring the possibility of restoring p53 function for therapeutic benefit. This review will highlight the key biochemical properties of p53 protein that affect its tumour-suppressor function and the experimental strategies that have been developed for the re-activation of the p53 pathway in cancers.

scholarly journals Lenvatinib Promotes the Antitumor Effects of Doxorubicin in Anaplastic Thyroid Cancer

2020 ◽  
Author(s):  
Xi Su ◽  
Jiaxin Liu ◽  
Haihong Zhang ◽  
Qingqing Gu ◽  
Xinrui Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Combination Therapy ◽  
Cell Cycle Arrest ◽  
Anaplastic Thyroid Cancer ◽  
Antitumor Efficacy ◽  
Potential Candidate ◽  
Antitumor Effects ◽  
Cycle Arrest

Abstract Background Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. It is one of the deadliest cancers in human due to the aggressive behavior and resistance to treatment. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating the patients with radioiodine-refractory differentiated thyroid cancer (DTC). However, antitumor efficacy of combination therapy with lenvatinib and doxorubicin remains largely unclear. Methods The antitumor efficacy of combination therapy with lenvatinib and doxorubicin on ATC cell proliferation and was assessed by the MTT assay and colony formation. Flow cytometry were employed to assess ATC cells’ apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Result Lenvatinib monotherapy was less effective than doxorubicin in treating ATC cell lines and xenografts model. The combination therapy of lenvatinib and doxorubicin significantly inhibited ATC cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest in compared to lenvatinib or doxorubicin monotherapy. Conclusion Lenvatinib promotes the antitumor effects of doxorubicin in ATC cell and xenografts model. Lenvatinib/doxorubicin combination may be a potential candidate therapeutic approach for ATC.

scholarly journals Role of Advanced Glycation End-Products and Other Ligands for AGE Receptors in Thyroid Cancer Progression

2021 ◽  
Vol 10 (18) ◽  
pp. 4084
Author(s):  
Agnieszka Bronowicka-Szydełko ◽  
Łukasz Kotyra ◽  
Łukasz Lewandowski ◽  
Andrzej Gamian ◽  
Irena Kustrzeba-Wójcicka
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Advanced Glycation End Products ◽  
Intracellular Signaling ◽  
Anaplastic Thyroid Cancer ◽  
Carbonyl Stress ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

To date, thyroid cancers (TCs) remain a clinical challenge owing to their heterogeneous nature. The etiopathology of TCs is associated not only with genetic mutations or chromosomal rearrangements, but also non-genetic factors, such as oxidative-, nitrosative-, and carbonyl stress-related alterations in tumor environment. These factors, through leading to the activation of intracellular signaling pathways, induce tumor tissue proliferation. Interestingly, the incidence of TCs is often coexistent with various simultaneous mutations. Advanced glycation end-products (AGEs), their precursors and receptors (RAGEs), and other ligands for RAGEs are reported to have significant influence on carcinogenesis and TCs progression, inducing gene mutations, disturbances in histone methylation, and disorders in important carcinogenesis-related pathways, such as PI3K/AKT/NF-kB, p21/MEK/MPAK, or JAK/STAT, RAS/ERK/p53, which induce synthesis of interleukins, growth factors, and cytokines, thus influencing metastasis, angiogenesis, and cancer proliferation. Precursors of AGE (such as methylglyoxal (MG)) and selected ligands for RAGEs: AS1004, AS1008, and HMGB1 may, in the future, become potential targets for TCs treatment, as low MG concentration is associated with less aggressive anaplastic thyroid cancer, whereas the administration of anti-RAGE antibodies inhibits the progression of papillary thyroid cancer and anaplastic thyroid cancer. This review is aimed at collecting the information on the role of compounds, engaged in glycation process, in the pathogenesis of TCs. Moreover, the utility of these compounds in the diagnosis and treatment of TCs is thoroughly discussed. Understanding the mechanism of action of these compounds on TCs pathogenesis and progression may potentially be the grounds for the development of new treatment strategies, aiming at quality-of-life improvements.

scholarly journals Antitumor effects of anlotinib in thyroid cancer

2019 ◽  
Vol 26 (1) ◽  
pp. 153-164 ◽  
Author(s):  
Xianhui Ruan ◽  
Xianle Shi ◽  
Qiman Dong ◽  
Yang Yu ◽  
Xiukun Hou ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Anaplastic Thyroid Cancer ◽  
Cancer Type ◽  
Papillary Thyroid ◽  
Antitumor Effects ◽  
Effective Therapeutic Strategy

There is no effective treatment for patients with poorly differentiated papillary thyroid cancer or anaplastic thyroid cancer (ATC). Anlotinib, a multi-kinase inhibitor, has already shown antitumor effects in various types of carcinoma in a phase I clinical trial. In this study, we aimed to better understand the effect and efficacy of anlotinib against thyroid carcinoma cells in vitro and in vivo. We found that anlotinib inhibits the cell viability of papillary thyroid cancer and ATC cell lines, likely due to abnormal spindle assembly, G2/M arrest, and activation of TP53 upon anlotinib treatment. Moreover, anlotinib suppresses the migration of thyroid cancer cells in vitro and the growth of xenograft thyroid tumors in mice. Our data demonstrate that anlotinib has significant anticancer activity in thyroid cancer, and potentially offers an effective therapeutic strategy for patients of advanced thyroid cancer type.

scholarly journals Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells

2006 ◽  
Vol 191 (2) ◽  
pp. 465-472 ◽  
Author(s):  
Maria G Catalano ◽  
Nicoletta Fortunati ◽  
Mariateresa Pugliese ◽  
Roberta Poli ◽  
Ornella Bosco ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Thyroid Cancer ◽  
Histone Deacetylase ◽  
Topoisomerase Ii ◽  
Human Cancer ◽  
Combined Therapy ◽  
Survival Rates ◽  
Hdac Inhibitors ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Thyroid Carcinoma

Multimodality treatments (i.e. surgery, chemotherapy, and radiotherapy) are recommended for anaplastic thyroid carcinoma (ATC), an extremely lethal human cancer, but to date there is little evidence that such approaches improve survival rates. It is thus necessary to seek new therapeutic tools. Histone deacetylase (HDAC) inhibitors are a promising class of anti-neoplastic agents that induce differentiation and apoptosis. Moreover, they may enhance the cytotoxicity of drugs targeting DNA through acetylation of histones. Using two ATC cell lines (CAL-62 and ARO), we show here that valproic acid (VPA), a clinically available HDAC inhibitor, enhances the activity of doxorubicin, whose anti-tumor properties involve binding to DNA and inhibiting topoisomerase II. A meager 0.7 mM VPA, which corresponds to serum concentrations in patients treated for epilepsy, is able to increase the cytotoxicity of doxorubicin about threefold in CAL-62 cells and twofold in ARO cells. The sensitizing effect, which is through histone acetylation, involves increased apoptosis, which is also shown by the increased caspase 3 activation and the enhancement of doxorubicin-induced G2 cell cycle arrest. These results might offer a rationale for clinical studies of a new combined therapy in an effort to improve the outcome of patients with anaplastic thyroid cancer.

Additive antitumor effects of gefitinib and imatinib on anaplastic thyroid cancer cells

2006 ◽  
Vol 58 (4) ◽  
pp. 460-470 ◽  
Author(s):  
Junichi Kurebayashi ◽  
Sumiko Okubo ◽  
Yutaka Yamamoto ◽  
Masahiko Ikeda ◽  
Katsuhiro Tanaka ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Anaplastic Thyroid Cancer ◽  
Antitumor Effects ◽  
Thyroid Cancer Cells

scholarly journals Effects of Dihydrotanshinone I on Proliferation and Invasiveness of Paclitaxel-Resistant Anaplastic Thyroid Cancer Cells

2021 ◽  
Vol 22 (15) ◽  
pp. 8083
Author(s):  
Lorenzo Allegri ◽  
Francesca Capriglione ◽  
Valentina Maggisano ◽  
Giuseppe Damante ◽  
Federica Baldan
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Current Treatment ◽  
Palliative Surgery ◽  
Therapeutic Approaches ◽  
Antitumor Effects ◽  
Aggressive Form ◽  
Thyroid Cancer Cells ◽  
Resistant Cells

ATC is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. In patients without known genetic aberrations, the current treatment is still represented by palliative surgery and systemic mono- or combined chemotherapy, which is often not fully effective for the appearance of drug resistance. Comprehension of the mechanisms involved in the development of the resistance is therefore an urgent issue to suggest novel therapeutic approaches for this very aggressive malignancy. In this study, we created a model of anaplastic thyroid cancer (ATC) cells resistant to paclitaxel and investigated the characteristics of these cells by analyzing the profile of gene expression and comparing it with that of paclitaxel-sensitive original ATC cell lines. In addition, we evaluated the effects of Dihydrotanshinone I (DHT) on the viability and invasiveness of paclitaxel-resistant cells. ATC paclitaxel-resistant cells highlighted an overexpression of ABCB1 and a hyper-activation of the NF-κB compared to sensitive cells. DHT treatment resulted in a reduction of viability and clonogenic ability of resistant cells. Moreover, DHT induces a decrement of NF-κB activity in SW1736-PTX and 8505C-PTX cells. In conclusion, to the best of our knowledge, the results of the present study are the first to demonstrate the antitumor effects of DHT on ATC cells resistant to Paclitaxel in vitro.

scholarly journals Anaplastic thyroid cancer. Is there a light at the end of the tunnel?

2020 ◽  
Vol 10 (1) ◽  
pp. 10-19 ◽  
Author(s):  
A. L. Pylev ◽  
A. A. Zhandarova ◽  
K. S. Petrov ◽  
D. S. Romanov ◽  
V. A. Lisovoy ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Thyroid Cancer ◽  
Primary Tumor ◽  
Molecular Genetic ◽  
Poor Response ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Tumor ◽  
Surgical Removal ◽  
Genetic Characteristics ◽  
Treatment Methods

Anaplastic thyroid cancer is one of the most prognostically unfavorable tumors. This disadvantage traditionally consisted of a rapid increase in the size of the primary tumor with a tendency to the development of asphyxia and the rapid appearance of distant metastases, as well as a poor response to the recommended treatment methods. The result of many years of efforts by oncologists around the world were several treatment regimens, including an ideal amount of surgical intervention, chemotherapy and radiation therapy, but the effectiveness of this treatment, as well as the patient’s life expectancy after it, could not be called satisfactory. Improving the understanding of the molecular genetic characteristics of tumors, including anaplastic thyroid cancer, provided us with information on two possible features of the genetic apparatus of tumor cells that can have clinical significance: V600E mutations in the BRAF gene and fusion of NTRK genes. The clinical example described in this article is probably the first Russian illustration of the effectiveness of anti-BRAF therapy in a patient with anaplastic thyroid cancer. From our point of view, the benefit of this example is not only to demonstrate the effectiveness of modern targeted therapy, but also the need not to abandon other treatment methods, in this case, radiation therapy to the area of the primary tumor (and by analogy with this, surgical removal of the thyroid tumor glands in case of its resectability).

Sign in / Sign up

Export Citation Format

Share Document