scholarly journals Advances in Biomarker-Driven Targeted Therapies in Thyroid Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6194
Author(s):  
Prachi Mishra ◽  
Dipranjan Laha ◽  
Robert Grant ◽  
Naris Nilubol
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Mapk Pathway ◽  
Treatment Strategies ◽  
Disease Recurrence ◽  
Receptor Kinase ◽  
New Treatment ◽  
Tyrosine Receptor Kinase ◽  
Multiple Receptor

Thyroid cancer is the most common type of endocrine malignancy comprising 2–3% of all cancers, with a constant rise in the incidence rate. The standard first-line treatments for thyroid cancer include surgery and radioactive iodine ablation, and a majority of patients show a good response to these therapies. Despite a better response and outcome, approximately twenty percent of patients develop disease recurrence and distant metastasis. With improved knowledge of molecular dysregulation and biological characteristics of thyroid cancer, the development of new treatment strategies comprising novel targets has accelerated. Biomarker-driven targeted therapies have now emerged as a trend for personalized treatments in patients with advanced cancers, and several multiple receptor kinase inhibitors have entered clinical trials (phase I/II/III) to evaluate their safety and efficacy. Most extensively investigated and clinically approved targeted therapies in thyroid cancer include the tyrosine receptor kinase inhibitors that target antiangiogenic markers, BRAF mutation, PI3K/AKT, and MAPK pathway components. In this review, we focus on the current advances in targeted mono- and combination therapies for various types of thyroid cancer.

Neurotrophic tyrosine kinase inhibitors: A review of implications for patients, clinicians and healthcare services

2020 ◽  
Vol 26 (8) ◽  
pp. 2015-2019
Author(s):  
Andrew Walker
Keyword(s):  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Healthcare Providers ◽  
Healthcare Services ◽  
New Approach ◽  
Regulatory Bodies ◽  
Targeted Agent ◽  
Tyrosine Receptor Kinase ◽  
To Receive

Neurotrophic tyrosine receptor kinase (NTRK) inhibitors represent the latest advancement as a treatment option in targeted therapies for malignant disease. NTRK gene fusions involving NTRK1, 2 or 3 are implicated as genetics drivers for a number of tumour types which arise within adult and paedatric patients. NTRK inhibitors (Larotrectinib and Entrectinib) are effective agents which have demonstrated clinical benefit in the treatment of NTRK fusion positive solid tumours. Larotrectinib represents the first targeted agent to receive approval from international authorisation and commissioning bodies for the treatment of a specific genetic expression indiscriminate of the site from which the tumour has arisen. As such NTRK inhibitors could pave the way for international healthcare bodies to adopt a similar approach for future targeted therapies thereby altering the manner in which healthcare providers and patients are able to access and utilise innovative, targeted treatment options in future. The potential implications of this new approach are likely to impact upon several aspects of the traditional authorisation and commissioning pathways with potential changes to the design of clinical trials, the review and approval process by regulatory bodies and immunohistopathology services.

scholarly journals Treatment of advanced thyroid cancer with targeted therapies: ten years of experience

2016 ◽  
Vol 23 (4) ◽  
pp. R185-R205 ◽  
Author(s):  
David Viola ◽  
Laura Valerio ◽  
Eleonora Molinaro ◽  
Laura Agate ◽  
Valeria Bottici ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Survival Rates ◽  
Current Status ◽  
Thyroid Cancers ◽  
Poorly Differentiated ◽  
Advanced Thyroid Cancer ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers

AbstractThyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15–20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.

The Pathobiology and Treatment of Hodgkin Lymphoma. Where do We go from Gianni Bonadonna's Lesson?

2017 ◽  
Vol 103 (2) ◽  
pp. 101-113 ◽  
Author(s):  
Simonetta Viviani ◽  
Valentina Tabanelli ◽  
Stefano A. Pileri
Keyword(s):  
Hodgkin Lymphoma ◽  
Targeted Therapies ◽  
Early Stage ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Diagnosis And Treatment ◽  
Molecular Characteristics ◽  
Seminal Contribution ◽  
Molecular Information ◽  
New Treatment

This article reviews the evolution of the diagnosis and treatment of Hodgkin lymphoma (HL) since its discovery in 1832. The morphological, phenotypic and molecular characteristics of both nodular lymphocyte-predominant HL and classical HL are revised in the light of recent molecular information and possible impact on the identification of risk groups as well as the use of targeted therapies. The seminal contribution of Gianni Bonadonna to developing new treatment strategies for both advanced and early-stage HL is highlighted.

scholarly journals New Treatment in Advanced Thyroid Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Dario Giuffrida ◽  
Angela Prestifilippo ◽  
Alessia Scarfia ◽  
Daniela Martino ◽  
Stefania Marchisotta
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Target Therapy ◽  
Endocrine Tumor ◽  
Thyroid Carcinomas ◽  
New Treatment ◽  
Reported Data ◽  
New Treatments ◽  
Embase Database ◽  
Effective Result

Thyroid cancer is the most common endocrine tumor. Thyroidectomy, radioactive iodine, and TSH suppression represent the standard treatment for differentiated thyroid cancer. Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. In this paper, we reviewed the recent literature reports (pubmed, medline, EMBASE database, and abstracts published in meeting proceedings) on new treatments in advanced nonmedullary and medullary thyroid carcinomas. Studies of many tyrosine kinase inhibitors as well as antiangiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. We summarized both the results obtained and the toxic effects associated with these treatments reported in clinical trials. Reported data in this paper are encouraging, but further trials are necessary to obtain a more effective result in thyroid carcinoma treatment.

Medullary Thyroid Cancer

2018 ◽  
Author(s):  
Geeta Lal
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitors ◽  
The United States ◽  
C Cells ◽  
Medullary Thyroid ◽  
Key Words Genetics ◽  
Thyroid C Cells ◽  
Men 2A

Medullary thyroid cancer (MTC) arises from the thyroid C-cells and accounts for 1 to 2% of thyroid cancers in the United States. Most tumors are sporadic but may occur as a part of the familial syndromes multiple endocrine neoplasia (MEN) 2A, MEN2B, and familial MTC. Surgery is the mainstay of treatment of these tumors, although recent advances in molecular genetics have enabled the development and use of targeted therapies such as tyrosine kinase inhibitors to treat patients with symptomatic metastatic disease.  This review contains 2 figures, 3 tables and 34 references Key Words: genetics, management, medullary thyroid cancer, MEN2A, MEN2B, targeted therapies

Medullary Thyroid Cancer

2018 ◽  
Author(s):  
Geeta Lal
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitors ◽  
The United States ◽  
C Cells ◽  
Medullary Thyroid ◽  
Key Words Genetics ◽  
Thyroid C Cells ◽  
Men 2A

Medullary thyroid cancer (MTC) arises from the thyroid C-cells and accounts for 1 to 2% of thyroid cancers in the United States. Most tumors are sporadic but may occur as a part of the familial syndromes multiple endocrine neoplasia (MEN) 2A, MEN2B, and familial MTC. Surgery is the mainstay of treatment of these tumors, although recent advances in molecular genetics have enabled the development and use of targeted therapies such as tyrosine kinase inhibitors to treat patients with symptomatic metastatic disease.  This review contains 2 figures, 3 tables and 34 references Key Words: genetics, management, medullary thyroid cancer, MEN2A, MEN2B, targeted therapies

scholarly journals Modern approaches to the treatment of radioiodine-refractory differentiated thyroid cancer

2021 ◽  
Vol 12 (1) ◽  
pp. 35-48
Author(s):  
D. Dzhuzha ◽  
S. Myasoyedov
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Targeted Therapies ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Radioiodine Therapy ◽  
The Poor ◽  
Post Operation

Radioiodine therapy is the main post-operation method of treatment of advanced differentiated thyroid cancer, but the loss of ability of iodine uptake causes the poor prognosis. The follow-up of patients with radioiodine-refractory differentiated thyroid cancer (RRDTC) is a serious problem. In review the definition, genesis, diagnostics and treatment of RRDTC were revealed. Taking into account the ineffectiveness of traditional methods of redifferentiation therapy, the perspectives of administration of targeted therapies with tyrosine kinase inhibitors were showed. Key words: radioiodine-refractory differentiated thyroid cancer, radioiodine therapy, targeted therapies with tyrosine kinase inhibitors.

scholarly journals Endocrine Toxicities of Antineoplastic Therapy

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 294
Author(s):  
Giulia Puliani ◽  
Marialuisa Appetecchia
Keyword(s):  
Tyrosine Kinase ◽  
Solid Tumors ◽  
Tyrosine Kinase Inhibitors ◽  
Antineoplastic Therapy ◽  
Kinase Inhibitors ◽  
Treatment Strategies ◽  
New Treatment

In recent years, the prognosis of many solid tumors has improved markedly thanks to new treatment strategies, including tyrosine kinase inhibitors (TKIs) and immunotherapy [...]

scholarly journals BRAF Inhibitors Induce Feedback Activation of RAS Pathway in Thyroid Cancer Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5744
Author(s):  
Elisa Bonaldi ◽  
Chiara Gargiuli ◽  
Loris De Cecco ◽  
Arianna Micali ◽  
Maria Grazia Rizzetti ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Mapk Pathway ◽  
Enrichment Analysis ◽  
Global Gene Expression ◽  
Gene Set Enrichment Analysis ◽  
Specific Gene ◽  
Ras Signaling ◽  
Braf Inhibitors ◽  
Oncogenic Mutation

BRAFV600E is the most frequent oncogenic mutation identified in papillary thyroid cancer (PTC). In PTC patients who do not respond to standard treatment, BRAF inhibitors are currently tested as alternative strategies. However, as observed for other targeted therapies, patients eventually develop drug resistance. The mechanisms of BRAF inhibitors response are still poorly understood in a thyroid cancer (TC) context. In this study, we investigated in BRAFV600E mutated TC cell lines the effects of Vemurafenib and Dabrafenib, two BRAF inhibitors currently used in a clinical setting. We assessed cell proliferation, and the expression and activity of the thyroid function related transporter NIS following the treatment with BRAF inhibitors. In addition, we investigated the global gene expression by microarray, the relevant modulated biological processes by gene set enrichment analysis (GSEA), and TC specific gene signatures related to MAPK pathway activation, thyroid differentiation, and transcriptional profile associated with BRAFV600E or RAS mutation. We found that both inhibitors induce antiproliferative and redifferentiative effects on TC cells, as well as a rewiring of the MAPK pathway related to RAS signaling. Our results suggest a possible mechanism of drug response to the BRAF inhibitors Vemurafenib or Dabrafenib, supporting very recent findings in TC patients treated with targeted therapies.

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