scholarly journals HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: The state of science in medullary thyroid carcinoma: current challenges and unmet needs

2020 ◽  
Vol 27 (8) ◽  
pp. T27-T39
Author(s):  
Ramona Dadu ◽  
Rozita Bagheri-Yarmand ◽  
Matthew D Ringel ◽  
Elizabeth G Grubbs ◽  
Mark Zafereo ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Unmet Needs ◽  
The State ◽  
Endocrine Tumors ◽  
Medullary Thyroid ◽  
Men 2 ◽  
Current State ◽  
Workshop Model ◽  
Working Groups

The 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) held in Houston, TX, USA, focused on emerging topics in the pathogenesis and therapy of malignant endocrine tumors associated with MEN syndromes. With MEN-2 syndromes, the most common malignancy is medullary thyroid carcinoma (MTC). In the spirit of the original MEN meeting workshop model, the conference included didactic lectures and interactive working groups of clinicians and researchers focused on the state of science in MTC and ongoing challenges or unmet needs in the understanding of MTC and to develop strategies to address these issues.

scholarly journals RET as a Diagnostic and Therapeutic Target in Sporadic and Hereditary Endocrine Tumors

2006 ◽  
Vol 27 (5) ◽  
pp. 535-560 ◽  
Author(s):  
Jan Willem B. de Groot ◽  
Thera P. Links ◽  
John T. M. Plukker ◽  
Cornelis J. M. Lips ◽  
Robert M. W. Hofstra
Keyword(s):  
Thyroid Carcinoma ◽  
Tyrosine Kinase ◽  
Medullary Thyroid Carcinoma ◽  
Therapeutic Option ◽  
Dominant Negative ◽  
Tyrosine Kinase Domain ◽  
Endocrine Tumors ◽  
Medullary Thyroid ◽  
Familial Medullary Thyroid Carcinoma ◽  
Men 2

The RET gene encodes a receptor tyrosine kinase that is expressed in neural crest-derived cell lineages. The RET receptor plays a crucial role in regulating cell proliferation, migration, differentiation, and survival through embryogenesis. Activating mutations in RET lead to the development of several inherited and noninherited diseases. Germline point mutations are found in the cancer syndromes multiple endocrine neoplasia (MEN) type 2, including MEN 2A and 2B, and familial medullary thyroid carcinoma. These syndromes are autosomal dominantly inherited. The identification of mutations associated with these syndromes has led to genetic testing to identify patients at risk for MEN 2 and familial medullary thyroid carcinoma and subsequent implementation of prophylactic thyroidectomy in mutation carriers. In addition, more than 10 somatic rearrangements of RET have been identified from papillary thyroid carcinomas. These mutations, as those found in MEN 2, induce oncogenic activation of the RET tyrosine kinase domain via different mechanisms, making RET an excellent candidate for the design of molecular targeted therapy. Recently, various kinds of therapeutic approaches, such as tyrosine kinase inhibition, gene therapy with dominant negative RET mutants, monoclonal antibodies against oncogene products, and nuclease-resistant aptamers that recognize and inhibit RET have been developed. The use of these strategies in preclinical models has provided evidence that RET is indeed a potential target for selective cancer therapy. However, a clinically useful therapeutic option for treating patients with RET-associated cancer is still not available.

scholarly journals Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives

2019 ◽  
Vol 26 (9) ◽  
pp. R499-R518 ◽  
Author(s):  
Lucieli Ceolin ◽  
Marta Amaro da Silveira Duval ◽  
Antônio Felippe Benini ◽  
Carla Vaz Ferreira ◽  
Ana Luiza Maia
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Intracellular Signaling ◽  
Progression Free Survival ◽  
Thyroid Neoplasms ◽  
Rare Type ◽  
Medullary Thyroid ◽  
Men 2 ◽  
Thyroid C Cells ◽  
Molecular Therapies

Medullary thyroid carcinoma (MTC) is a rare type of tumor that originates from thyroid C cells and accounts for 2–4% of all malignant thyroid neoplasms. MTC may occur sporadically or be inherited, as part of the MEN 2 syndrome. Germline mutations of the RET (REarranged during Transfection) proto-oncogene cause hereditary cancer, whereas somatic RET mutations and, less frequently, RAS mutations have been described in sporadic MTC samples. Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC. Nevertheless, despite recent advances, the management of advanced, progressive MTC remains challenging. The multikinase inhibitors (MKI), vandetanib and cabozantinib, were approved for the treatment of progressive or symptomatic MTC, and several other compounds have exhibited variable efficacy. Although these drugs have been shown to improve progression-free survival, no MKI has been shown to increase the overall survival. As these drugs are nonselective, significant off-target toxicities may occur, limiting achievement of the required TK-specific inhibition. Recently, next-generation small-molecule TKI has been developed. These TKI are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. Here, we summarize the current understanding of the intracellular signaling pathways involved in MTC pathogenesis as well as the therapeutic approaches and challenges for the management of advanced MTC, focusing on targeted molecular therapies.

Ultrastructural Evaluation of Parathyroid Glands from Bulls with Ultimobranchial Thyroid Tumors

1974 ◽  
Vol 32 ◽  
pp. 44-45
Author(s):  
J. T. Yarrington ◽  
C. C. Capen ◽  
H. E. Black
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Parathyroid Glands ◽  
Endocrine Tumors ◽  
Thyroid Tumors ◽  
Medullary Thyroid ◽  
Skeletal Disease ◽  
Calcium Phosphorus ◽  
Age Range ◽  
Parathyroid Gland Activity

A syndrome of ultimobranchial thyroid tumors (UTT) of aged bulls shares many characteristics with medullary thyroid carcinoma in man (Black et al. Cancer 32:867-878, 1973). Multiple endocrine tumors (pheochromocytomas, pituitary adenomas) and severe skeletal disease (vertebral osteosclerosis with ankylosing spondylosis and degenerative osteoarthrosis) often are detected coincidentally in bulls with UTT. Parathyroid hyperplasia or chief cell adenomas have been reported to occur frequently in humans with familial medullary thyroid carcinoma. However, parathyroid gland activity in bulls with UTT has not been well characterized. The objectives of this investigation were: (1) to investigate the histopathologic and ultrastructural alterations in parathyroid glands of bulls with UTT compared to control bulls of the same age range without C-cell tumors, and (2) to correlate these morphologic findings in the parathyroids with changes in serum calcium, phosphorus, and immunoreactive parathyroid hormone.

Multiple endocrine neoplasia type 2

2011 ◽  
pp. 951-953
Author(s):  
Niamh M. Martin ◽  
Karim Meeran ◽  
Stephen R. Bloom
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Medullary Thyroid ◽  
Men 2 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A

Multiple endocrine neoplasia type 2 (MEN 2) is a rare cancer susceptibility syndrome which has at least three distinct variants: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). The syndrome was first described by John Sipple in 1961 (1). The features of MEN 2A and its clinical variants are outlined in Box 6.12.1. Medullary thyroid carcinoma (MTC) is seen in all variants of MEN 2A and is frequently the earliest neoplastic manifestation, reflecting its earlier and overall higher penetrance. MEN 2 is due to the autosomal dominant inheritance of a germline missense mutation in the ‘hot-spot’ regions of the rearranged during transfection (RET) (OMIM 164761) proto-oncogene (2, 3). MEN 2 has an estimated prevalence of 1:30 000, with MEN 2A accounting for more than 75% of cases. The introduction of RET screening in family members of affected individuals has significantly altered the clinical outcome of MEN 2, by allowing prophylactic surgery for MTC, and screening enabling early intervention for phaeochromocytoma (4, 5). Prior to the availability of genetic screening, more that half of MEN 2 affected individuals died before or during the fifth decade from metastatic MTC or cardiovascular complications from an underlying phaeochromocytoma.

scholarly journals Role of genetic diagnosis in thyroid neoplasms

2019 ◽  
pp. 40-42
Author(s):  
Vaktangova N ◽  
Garcia Castañon S ◽  
Martinez Gago ◽  
Corrales B ◽  
Rodríguez Aguilar R
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Genetic Diagnosis ◽  
Malignant Neoplasm ◽  
Thyroid Neoplasms ◽  
Prophylactic Surgery ◽  
Early Age ◽  
Medullary Thyroid ◽  
Men 2

Carcinoma medullary thyroid is a rare, malignant neoplasm. Affected patients can be hereditary carriers, but in most cases they are spontaneously affected. In hereditary cases, prophylactic surgery is recommended at an early age. We present a case of the patient carrier of mutation of the proto-oncogene type RET with medullary thyroid carcinoma prophylactic surgery already in adulthood. Keywords: Medullary thyroid carcinoma; MEN 2; Prophylactic surgery

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