scholarly journals Metastatic mechanisms in follicular cell-derived thyroid cancer

2013 ◽  
Vol 20 (6) ◽  
pp. R307-R319 ◽  
Author(s):  
John E Phay ◽  
Matthew D Ringel
Keyword(s):  
Thyroid Cancer ◽  
Poor Prognosis ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Distant Metastases ◽  
Anaplastic Thyroid Cancer ◽  
Current Data ◽  
Metastatic Progression ◽  
Primary Tumors ◽  
Regional Metastases

Thyroid cancer incidence is rising annually largely related to enhanced detection and early stage well-differentiated primary tumors. The prognosis for patients with early stage thyroid cancer is outstanding with most patients being cured with surgery. In selected cases, I-131 is administered to treat known or suspected residual or metastatic disease. Even patients with loco-regional metastases typically have an outstanding long-term prognosis, albeit with monitoring and occasional intervention for residual or recurrent disease. By contrast, individuals with distant metastases from thyroid cancer, particularly older patients with larger metastatic burdens and those with poorly differentiated tumors, have a poor prognosis. Patients with metastatic anaplastic thyroid cancer have a particularly poor prognosis. Published clinical trials indicate that transient disease control and partial remissions can be achieved with kinase inhibitor therapy directed toward angiogenic targets and that in some cases I-131 uptake can be enhanced. However, the direct targets of activity in metastatic lesions are incompletely defined and clear evidence that these treatments increase the duration or quality of life of patients is lacking, underscoring the need for improved knowledge regarding the metastatic process to inform the development of new therapies. In this review, we will focus on current data and hypotheses regarding key regulators of metastatic dormancy, metastatic progression, and the role of putative cancer stem cells.

scholarly journals Scalp Metastasis of Mesothelioma

2021 ◽  
Author(s):  
İlkin Yetişkin ◽  
Berna Eren Kömürcüoğlu ◽  
Eylem Yıldırım
Keyword(s):  
Adrenal Gland ◽  
Malignant Mesothelioma ◽  
Malignant Tumor ◽  
Late Stage ◽  
Poor Prognosis ◽  
Early Stage ◽  
Asbestos Exposure ◽  
Distant Metastases ◽  
Rare Neoplasm ◽  
Scalp Metastasis

Mesothelioma is a primary malignant tumor of the mesothelial cells lining the pleura, pericardium and peritoneum, which is frequently seen between the ages of 40-60. Malignant mesothelioma (MM) is a rare neoplasm with a poor prognosis, usually associated with asbestos exposure. It is characterized by aggressive local invasion and metastatic spread. Extrathoracic lymphogenous-hematogenous metastases are rare at the time of diagnosis and in the early stage. However, metastases develop in at least half of the cases in the late stage of the disease. After the spread of serous membranes, distant metastases to the bone, adrenal gland, and liver are frequently observed. Skin and scalp metastases are rarely observed. Our case MPM is presented because it is a rare scalp metastasis.

scholarly journals Late-onset distant metastases confer poor prognosis in patients with well-differentiated thyroid cancer

Gland Surgery ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1857-1866
Author(s):  
Chan Kwon Jung ◽  
Sohee Lee ◽  
Ja Seong Bae ◽  
Dong-Jun Lim
Keyword(s):  
Thyroid Cancer ◽  
Poor Prognosis ◽  
Differentiated Thyroid Cancer ◽  
Late Onset ◽  
Distant Metastases ◽  
Well Differentiated

scholarly journals Targeting XPO1 and PAK4 in 8505C Anaplastic Thyroid Cancer Cells: Putative Implications for Overcoming Lenvatinib Therapy Resistance

2019 ◽  
Vol 21 (1) ◽  
pp. 237 ◽  
Author(s):  
Husain Yar Khan ◽  
James Ge ◽  
Misako Nagasaka ◽  
Amro Aboukameel ◽  
Gabriel Mpilla ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Rho Gtpase ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Anaplastic Thyroid Cancer ◽  
Therapy Resistance ◽  
Molecular Profile ◽  
The Impact ◽  
Thyroid Cancer Cells

Lenvatinib is a multitargeted tyrosine kinase inhibitor (TKI) that shows improved median progression-free survival (PFS) in patients with thyroid carcinomas. However, virtually all patients ultimately progress, indicating the need for a better understanding of the mechanisms of resistance. Here, we examined the molecular profile of anaplastic thyroid cancer cells (8505C) exposed to lenvatinib and found that long-term exposure to lenvatinib caused phenotypic changes. Consistent with change toward mesenchymal morphology, activation of pro-survival signaling, nuclear exporter protein exportin 1 (XPO1) and Rho GTPase effector p21 activated kinases (PAK) was also observed. RNA-seq analysis showed that prolonged lenvatinib treatment caused alterations in numerous cellular pathways and several oncogenes such as CEACAM (carcinoembryonic antigen-related cell adhesion molecule) and NUPR1 (Nuclear protein 1) were also upregulated. Further, we evaluated the impact of XPO1 and PAK4 inhibition in the presence or absence of lenvatinib. Targeted inhibition of XPO1 and PAK4 could sensitize the 8505C cells to lenvatinib. Both XPO1 and PAK4 inhibitors, when combined with lenvatinib, showed superior anti-tumor activity in 8505C sub-cutaneous xenograft. These studies bring forward novel drug combinations to complement lenvatinib for treating anaplastic thyroid cancer. Such combinations may possibly reduce the chances of lenvatinib resistance in thyroid cancer patients.

scholarly journals Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond

2019 ◽  
Vol 40 (6) ◽  
pp. 1573-1604 ◽  
Author(s):  
Maria E Cabanillas ◽  
Mabel Ryder ◽  
Camilo Jimenez
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Rapid Evolution ◽  
Anaplastic Thyroid Cancer ◽  
The Us ◽  
Advanced Thyroid Cancer ◽  
Inhibitor Drug ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract The treatment of advanced thyroid cancer has undergone rapid evolution in the last decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer and a number of other commercially available drugs that have been studied for this indication. Although most of the US Food and Drug Administration (FDA)–approved drugs are antiangiogenic multikinase inhibitors—vandetanib, cabozantinib, sorafenib, lenvatinib—there are two FDA indications that are mutation specific—dabrafenib/trametinib for BRAF-mutated anaplastic thyroid cancer and larotrectinib for NTRK-fusion thyroid cancer. Furthermore, other mutation-specific drugs, immunotherapies, and novel strategies for advanced thyroid cancer are under investigation. Understanding the molecular basis of thyroid cancer, the drugs of interest for treatment of advanced thyroid cancer, and how these drugs can be administered safely and in the appropriate clinical scenario are the topics of this review.

scholarly journals A Case of Thyroid Papillary Carcinoma: Remarkable Decrease in Multiple Lung Metastases within 40 Years after a Single Administration of Radioiodine without Thyroidectomy and with Later Anaplastic Transformation

2017 ◽  
Vol 10 (3) ◽  
pp. 928-937 ◽  
Author(s):  
Chio Okuyama ◽  
Mitsuhiro Kimura ◽  
Minori Oda ◽  
Naohiro Kodani ◽  
Norihiro Aibe ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Total Thyroidectomy ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Distant Metastases ◽  
Anaplastic Thyroid Cancer ◽  
Anaplastic Carcinoma ◽  
High Rate ◽  
Childhood And Adolescence ◽  
Anaplastic Transformation

Differentiated thyroid carcinoma is an uncommon malignancy of childhood and adolescence that is unique because it has an overall favorable prognosis despite its relatively high rate of nodal and distant metastases. Total thyroidectomy and positive 131I therapy are recommended for cases with pulmonary metastases. In contrast, anaplastic thyroid cancer is one of the most aggressive malignancies that have an unfavorable and miserable prognosis. We report a case with an impressively long history. The patient had multiple pulmonary metastases that had been diagnosed by 131I administration when he was 14 years old, about 45 years before he underwent thyroidectomy. He had been kept unaware of his disease by his family and received no treatment for most of his life. Pulmonary nodules were noted at several medical checkups and showed a remarkable decrease in size during the untreated 44-year period after the 131I administration. At age 58, his thyroid cancer was first detected and total thyroidectomy was performed, with subsequent radioiodine therapy for pulmonary metastases. Unfortunately, anaplastic carcinoma developed and he died of disseminated tumors later.

Witnessing a New Era? – The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

2010 ◽  
Vol 8 (2) ◽  
pp. 122
Author(s):  
Jochen Lorch ◽  
Wieland Voigt ◽  
◽  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase Ii Trials ◽  
New Era ◽  
Cancer Subtypes

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signalling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomised Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarise the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

Witnessing a New Era?—The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

2012 ◽  
Vol 08 (02) ◽  
pp. 122
Author(s):  
Jochen Lorch ◽  
Wieland Voigt ◽  
◽  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Strategies ◽  
Anaplastic Thyroid Cancer ◽  
Phase Iii ◽  
Clinical Activity ◽  
Phase Ii Trials ◽  
New Era ◽  
Cancer Subtypes

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signaling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomized Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarize the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

scholarly journals Age as a Prognostic Factor in Anaplastic Thyroid Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Vladan Zivaljevic ◽  
Katarina Tausanovic ◽  
Ivan Paunovic ◽  
Aleksandar Diklic ◽  
Nevena Kalezic ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Thyroid Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Distant Metastases ◽  
Anaplastic Thyroid Cancer ◽  
Multivariate Regression Analysis ◽  
Rank Test ◽  
Cox Regression Analysis

Background.Anaplastic thyroid cancer (ATC) is one of the tumors with the shortest survival in human medicine.Aim.The aim was to determine the importance of age in survival of patients with ATC.Material and Methods. We analyzed the data on 150 patients diagnosed with ATC in the period from 1995 to 2006. The Kaplan-Meier method and log-rank test were used to determine overall survival. Prognostic factors were identified by univariate and multivariate Cox regression analysis.Results.The youngest patient was 35 years old and the oldest was 89 years old. According to univariate regression analysis, age was significantly associated with longer survival in patients with ATC. In multivariate regression analysis, patients age, presence of longstanding goiter, whether surgical treatment is carried out or not, type of surgery, tumor multicentricity, presence of distant metastases, histologically proven preexistent papillary carcinoma, radioiodine therapy, and postoperative radiotherapy were included. According to multivariate analysis, besides surgery (P=0.000, OR = 0.43, 95% CI = 0.29–0.63), only patients age (P=0.023, OR = 0.68, 95% CI = 0.49–0.95) was independent prognostic factor of favorable survival in patients with ATC.Conclusion. Age is a factor that was independently associated with survival time in ATC. Anaplastic thyroid cancer has the best prognosis in patients younger than 50 years.

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