1,850 results match your criteria Medullary Thyroid Cancer and RET

RET kinase inhibitors for -altered thyroid cancers.

Ther Adv Med Oncol 2022 21;14:17588359221101691. Epub 2022 Jun 21.

Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Precision oncology has opened a new era in cancer treatment focused on targeting specific cellular pathways directly involved in tumorigenesis. The REarrangement during Transfection () proto-oncogene is involved in the pathogenesis of various thyroid cancer subtypes. Mutations in give rise to both hereditary and sporadic medullary thyroid cancer (MTC). Read More

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Selpercatinib-Induced Hypothyroidism Through Off-Target Inhibition of Type 2 Iodothyronine Deiodinase.

JCO Precis Oncol 2022 Jun;6:e2100496

Department of Medicine, Division of Endocrinology, Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: The development of the selective RET inhibitors selpercatinib and pralsetinib has revolutionized the treatment of metastatic progressive RET-mutant medullary thyroid carcinoma (MTC) and other RET-driven cancers, given their more favorable side-effect profile. The aim of this study is to investigate the mechanisms of selpercatinib-induced thyroid dysfunction in athyreotic patients with RET-mutant MTC and in patients with RET-mutant non-small-cell lung cancer (NSCLC) who had a functional thyroid.

Materials And Methods: Thyroid hormone levels were evaluated in an observational cohort of five athyreotic patients with MTC and 30 patients with NSCLC before and after initiation of selpercatinib. Read More

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Medullary thyroid carcinoma: a narrative historical review.

Expert Rev Anticancer Ther 2022 Jun 22:1-12. Epub 2022 Jun 22.

Department of Surgery, St. Paul's Hospital & University of British Columbia, Vancouver, British Columbia, Canada.

Introduction: Sporadic or hereditary medullary thyroid carcinoma (MTC) is an uncommon thyroid malignancy arising from calcitonin secreting parafollicular C cells. Interestingly, MTC and calcitonin were distinct entities that were discovered independently yet concurrently, and their association was unknown.

Areas Covered: This review aims to present a historical review of the evolution of our understanding of MTC and its tumor marker calcitonin to highlight the prominent individuals that influenced and shaped our knowledge of this uncommon thyroid cancer type up to the dawn of the 21 century. Read More

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A novel germline deletion of p.C630 in RET causes MTC and promotes cell proliferation and sensitivity to pralsetinib.

J Clin Endocrinol Metab 2022 Jun 11. Epub 2022 Jun 11.

Department of Clinical Lab, Perking University Cancer Hospital and Institute, Beijing, 100142, PR. China.

Context: Medullary thyroid cancer (MTC) is usually caused by gain-of-function mutations in the proto-oncogene RET.

Objective: This study aimed to determine the underlying mechanism in a male patient diagnosed with the MTC at age 51 years.

Methods: Genomic DNA extracted from leukocytes or tumor tissues of patients was used for next-generation sequencing-based (NGS) panel sequencing and Sanger sequencing. Read More

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Multiple endocrine neoplasia type 2 and autoimmune polyendocrine syndromes (type 1 diabetes mellitus and Graves' disease) in a 16-year-old male with Kabuki syndrome.

Endocr J 2022 Jun 8. Epub 2022 Jun 8.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Multiple endocrine neoplasia type 2A (MEN2A) is caused by germline pathogenic variants in the RET proto-oncogene and is characterized by medullary thyroid cancer (MTC), pheochromocytoma, and hyperparathyroidism. Autoimmune polyendocrine syndromes (APS) are defined as multiple endocrine gland insufficiency associated with loss of immune tolerance. APS type 2 (APS-2) consists of at least two of the following diseases: type 1 diabetes mellitus (T1DM), autoimmune thyroid disease, and Addison's disease. Read More

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Observational study of population genomic screening for variants associated with endocrine tumor syndromes in a large, healthcare-based cohort.

BMC Med 2022 06 7;20(1):205. Epub 2022 Jun 7.

Genomic Medicine Institute, Geisinger, Danville, PA, USA.

Background: In current care, patients' personal and self-reported family histories are primarily used to determine whether genetic testing for hereditary endocrine tumor syndromes (ETS) is indicated. Population genomic screening for other conditions has increased ascertainment of individuals with pathogenic/likely pathogenic (P/LP) variants, leading to improved management and earlier diagnoses. It is unknown whether such benefits occur when screening broader populations for P/LP ETS variants. Read More

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Medullary Thyroid Cancer: An Experience from a Tertiary Care Hospital of a Developing Country.

Indian J Endocrinol Metab 2022 Jan-Feb;26(1):68-72. Epub 2022 Apr 27.

Department of Medicine, Section of Endocrinology, Aga Khan University Hospital, Karachi, Pakistan.

Background: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer that occasionally occurs as part of MEN2A. The universal treatment of MTC is total thyroidectomy with central lymph node dissection. For disease progression, carcinoembryonic antigen (CEA) and calcitonin (CTN) need to be followed. Read More

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Novel Therapeutics and Treatment Strategies for Medullary Thyroid Cancer.

Endocrinol Metab Clin North Am 2022 Jun 4;51(2):379-389. Epub 2022 May 4.

Department of Head and Neck Surgery, MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 1445, Houston, TX 77030, USA. Electronic address:

Medullary thyroid cancer is a rare thyroid malignancy with unique management considerations. In general, small intrathyroidal tumors are cured by total thyroidectomy with central compartment dissection, while large tumors and those with disease spread to regional lymph nodes and distant organs (most commonly lung, liver, and bone) are more difficult to cure. The last decade has seen significant progress in the treatment of advanced MTC, largely due to the discovery and availability of novel targeted therapies, including new drugs specifically targeting the RET protooncogone. Read More

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c.1901G>A and Novel Mutations in Familial Pheochromocytomas.

Genes (Basel) 2022 May 12;13(5). Epub 2022 May 12.

Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Beijing 100037, China.

Familial PHEOs (pheochromocytomas) are inherited as an autosomal dominant trait, and inherited PHEOs can be one clinical phenotype of clinical syndromes, such as multiple endocrine neoplasia type 2A (MEN2A). In recent years, there has been a lot of controversy about the factors affecting the penetrance of PHEOs in MEN2A, of which the effects of (rearranged during transfection) proto-oncogene mutations are the primary concern. In this report, we performed genetic screening of patients in one family presenting with PHEOs and found they carried a c. Read More

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Successful Treatment with Selpercatinib for Ectopic Cushing's Syndrome Due to Medullary Thyroid Cancer.

Curr Oncol 2022 05 12;29(5):3494-3498. Epub 2022 May 12.

Department of Oncology, Sahlgrenska University Hospital, SE-41302 Gothenburg, Sweden.

Selpercatinib, a RET kinase inhibitor, is an effective treatment for patients with medullary thyroid cancer with RET mutations. In this paper, we present the case of a 62-year-old man with ectopic Cushing's syndrome due to medullary thyroid cancer who received treatment with selpercatinib. Six months later, all the cushingoid features had resolved, and s-calcitonin had decreased from 580 pmol/L to 3. Read More

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Somatic Ret Indels In Sporadic Medullary Thyroid Cancer: Prevalence And Response To Selpercatinib.

J Clin Endocrinol Metab 2022 May 25. Epub 2022 May 25.

Unit of Endocrinology, Department of Clinical and Experimental Medicine, University-Hospital of Pisa, 56124 Pisa, Italy.

Context: Although the majority of RET alterations are single nucleotide variants (SNV), small deletions and/or insertions have been reported at variable prevalence. No information about the efficacy of RET specific inhibitors in patients harboring RET indels, has been provided.

Objective: To present an update on the prevalence of RET indels in MTC and describe the efficacy of selpercatinib in patients with advanced RET indels MTC. Read More

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Pralsetinib: chemical and therapeutic development with FDA authorization for the management of RET fusion-positive non-small-cell lung cancers.

Arch Pharm Res 2022 May 22;45(5):309-327. Epub 2022 May 22.

Department of Pharmaceutical Chemistry, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), DPSR University, New Delhi, India.

Pralsetinib (PRL) is a selective Rearranged during Transfection (RET) inhibitor, developed by Blueprint Medicines Corporation for the treatment of RET fusion non-small-cell lung cancer (NSCLC), papillary thyroid cancer (PTC), and medullary thyroid carcinoma (MTC). RET is a known proto-oncogene found in NSCLC, PTC, and MTC. PRL was recently granted accelerated USFDA approval with the brand name GAVRETO™ on 4 September 2020 to treat metastatic RET fusion-positive NSCLC and was updated on 1 December 2020 with the addition of advanced and metastatic RET-altered MTC and PTC in the USA. Read More

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T cells engineered to express immunoreceptors targeting the frequently expressed medullary thyroid cancer antigens calcitonin, CEA and RET M918T.

Thyroid 2022 May 19. Epub 2022 May 19.

Earle A Chiles Research Institute, 535763, PORTLAND, Oregon, United States;

Background: Medullary thyroid cancer (MTC) is a rare malignancy originating from the calcitonin-producing C cells of the thyroid. Despite recent therapeutic advances, metastatic MTC remains incurable. Adoptive cell therapy (ACT) using genetically engineered T cells targeting either tissue-restricted, tumor-associated antigens or mutated neoantigens has led to durable remissions in other metastatic solid tumors. Read More

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Is Encapsulated Medullary Thyroid Carcinoma Associated With a Better Prognosis? A Case Series and a Review of the Literature.

Front Endocrinol (Lausanne) 2022 27;13:866572. Epub 2022 Apr 27.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Context: Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine neoplasm that may spread to lymph nodes before the primary tumor is diagnosed; moreover, distant metastases are already present in about 10% of patients at diagnosis. Serum calcitonin (Ctn) usually reflects the spread of disease, thus orienting the extent of surgery and predicting the possibility of biochemical remission. Tumor size and vascular invasion are important prognostic factors, but little is known on the relationship between other histopathological features, such as the presence of a tumor capsule, and long term outcome of MTC. Read More

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Practical lessons from treating medullary thyroid carcinoma patients harboring a RET-alteration: Pralsetinib-induced acute confusional state.

Acta Oncol 2022 07 9;61(7):819-823. Epub 2022 May 9.

Neuroendocrine Tumor Unit, ENETS Center of Excellence, Endocrinology and Metabolism Department, Hadassah Medical Organization and Faculty of Medicine, Jerusalem, Israel.

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Diagnostic performance of next-generation sequencing and genetic profiling in thyroid nodules from a single center in China.

Eur Thyroid J 2022 May 27;11(3). Epub 2022 May 27.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Objective: The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodules by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules.

Methods: A total of 1039 FNA and surgical resection samples tested using the targeted multigene next-generation sequencing (NGS) panel were retrospectively collected. Read More

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Metastatic medullary thyroid carcinoma: a new way forward.

Endocr Relat Cancer 2022 May 31;29(7):R85-R103. Epub 2022 May 31.

Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK.

Medullary thyroid carcinoma (MTC) is a rare malignancy comprising 1-2% of all thyroid cancers in the United States. Approximately 20% of cases are familial, secondary to a germline RET mutation, while the remaining 80% are sporadic and also harbour a somatic RET mutation in more than half of all cases. Up to 15-20% of patients will present with distant metastatic disease, and retrospective series report a 10-year survival of 10-40% from time of first metastasis. Read More

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Pre- And Post-Operative Circulating Tumoral Dna In Patients With Medullary Thyroid Carcinoma.

J Clin Endocrinol Metab 2022 Apr 26. Epub 2022 Apr 26.

Unit of Endocrinology, Department of Clinical and Experimental Medicine, University-Hospital of Pisa, 56124 Pisa, Italy.

Context: Measurement of driver mutations in circulating tumoral DNA (ctDNA) obtained by liquid biopsy has been shown to be a sensitive biomarker in several human tumors.

Objective: The aim of this study was to evaluate the clinical relevance of pre- and post-operative ctDNA in sporadic medullary thyroid cancer (sMTC).

Methods: We studied pre- and post-operative ctDNA in 26 and 23 sMTC patients, respectively. Read More

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Medullary Thyroid Carcinoma Mutational Spectrum Update and Signaling-Type Inference by Transcriptional Profiles: Literature Meta-Analysis and Study of Tumor Samples.

Cancers (Basel) 2022 Apr 13;14(8). Epub 2022 Apr 13.

Molecular Mechanisms Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.

Medullary thyroid carcinoma (MTC) is a rare but aggressive tumor. Although and genes are recognized drivers in MTC, associated downstream signaling pathways are largely unknown. In this study, we report 17 sporadic MTCs, collected at our institution, comprising patient-matched primary and lymph node metastatic tumors investigated for mutational and transcriptional profiles. Read More

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"Incidentally discovered medullary thyroid carcinoma in the post-operative Graves' patient - A case report".

Am J Otolaryngol 2022 May-Jun;43(3):103450. Epub 2022 Apr 5.

Department of Otolaryngology - Head and Neck Surgery, University of Missouri School of Medicine, 1 Hospital Drive, Columbia, MO 65212, United States of America.

Objective: To report a very rare case of incidentally discovered Medullary Thyroid Carcinoma after total thyroidectomy in a patient with Graves' disease, review available literature, and present readers with management information.

Results: Medullary Thyroid Carcinoma in the setting of Graves' disease is a rare scenario. Only fifteen total cases besides ours has been described in literature, and only six other cases were incidentally discovered. Read More

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Sporadic Medullary Thyroid Carcinoma: Towards a Precision Medicine.

Front Endocrinol (Lausanne) 2022 29;13:864253. Epub 2022 Mar 29.

Department of Clinical and Experimental Medicine, Endocrine Unit, University Hospital of Pisa, Pisa, Italy.

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignant tumor originating from parafollicular C-cells producing calcitonin. Most of cases (75%) are sporadic while the remaining (25%) are hereditary. In these latter cases medullary thyroid carcinoma can be associated (multiple endocrine neoplasia type IIA and IIB) or not (familial medullary thyroid carcinoma), with other endocrine diseases such as pheochromocytoma and/or hyperparathyroidism. Read More

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Preoperative serum calcitonin may improve initial surgery for medullary thyroid cancer in patients with indeterminate cytology.

ANZ J Surg 2022 06 12;92(6):1428-1433. Epub 2022 Apr 12.

Monash University Endocrine Surgery Unit, Alfred Hospital, Melbourne, Victoria, Australia.

Background: Medullary thyroid cancer (MTC) is rare, with poorer outcomes than differentiated thyroid cancer. We aimed to identify areas for improvement in the pre-operative evaluation of patients with possible MTC in a high-volume endocrine surgery unit in accordance with current practice guidelines. We hypothesised that the selective use of serum calcitonin (sCT) as a biomarker for possible MTC could guide the extent of initial surgical management. Read More

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Clinical Application of Next-Generation Sequencing in Advanced Thyroid Cancers.

Thyroid 2022 Jun 16;32(6):657-666. Epub 2022 May 16.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.

With the emergence of mutation-based systemic therapies for patients with advanced thyroid cancer, molecular profiling has become an important component of care. Although next-generation sequencing (NGS) gene panels are accessible to clinicians, there is no consensus on the optimal approach to testing. This study investigates the clinical application of NGS results in the management of advanced thyroid cancer. Read More

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Resistance to RET targeted therapy in Thyroid Cancer: Molecular basis and overcoming strategies.

Cancer Treat Rev 2022 Apr 1;105:102372. Epub 2022 Mar 1.

Medical Oncology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain; The Ramon y Cajal Health Research Institute [IRYCIS], CIBERONC, 28034 Madrid, Spain; Medicine School, Alcalá University, 28805 Madrid, Spain. Electronic address:

Thyroid cancer is the most frequently diagnosed endocrine malignancy, with an increasing incidence over the last decades. The recent advances in understanding the molecular mechanisms underlying the carcinogenesis of thyroid cancer have led to a better therapeutic approach of these tumors. This has allowed the development and approval of several drugs during the past decade. Read More

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Analogs of the Heat Shock Protein 70 Inhibitor MKT-077 Suppress Medullary Thyroid Carcinoma Cells.

Int J Mol Sci 2022 Jan 19;23(3). Epub 2022 Jan 19.

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the proto-oncogene. We previously demonstrated that depletion of the mitochondrial molecular chaperone, mortalin, can effectively suppress human MTC cells in culture and in mouse xenografts, by disrupting mitochondrial bioenergetics and subsequently inducing apoptosis and RET downregulation. Similar effects were induced by MKT-077, a water-soluble rhodocyanine dye analog known to inhibit mortalin, but with notable toxicity in animals. Read More

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January 2022

Diagnostic characteristics, treatment patterns, and clinical outcomes for patients with advanced/metastatic medullary thyroid cancer.

Thyroid Res 2022 Feb 12;15(1). Epub 2022 Feb 12.

RTI Health Solutions, 307 Waverley Oaks Road, Waltham, MA, 02452, USA.

Background: Medullary thyroid cancer (MTC) accounts for approximately 1.6% of new cases of thyroid cancer. The objective of this study was to describe patient characteristics, biomarker testing, treatment patterns, and clinical outcomes among patients with advanced/metastatic MTC in a real-world setting in the United States and to identify potential gaps in the care of these patients. Read More

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February 2022

Sex differences in MEN 2A penetrance and expression according to parental inheritance.

Eur J Endocrinol 2022 Feb 25;186(4):469-476. Epub 2022 Feb 25.

Department of Visceral, Vascular and Endocrine Surgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

Objective: This study aimed to delineate the age-dependent clinical penetrance and expression of heterozygous rearranged during transfection (RET) missense mutations associated with multiple endocrine neoplasia 2A (MEN2A) according to parental inheritance.

Design: This was an observational study of RET carriers operated for MEN2A-associated tumors between 1985 and 2021.

Methods: Kaplan-Meier time-to-event and multivariable Cox proportional hazards regression analyses were performed on node metastases from medullary thyroid cancer, pheochromocytoma, bilateral pheochromocytoma, and primary hyperparathyroidism. Read More

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February 2022

Extension of Prophylactic Surgery in Medullary Thyroid Carcinoma. Differences Between Sporadic and Hereditary Tumours According to Calcitonin Levels and Lymph Node Involvement.

World J Surg 2022 04 28;46(4):820-828. Epub 2022 Jan 28.

Department of General Surgery, Hospital Universitario Ramón y Cajal, Ctra. Colmenar Viejo, Km 9.100., 28034, Madrid, Spain.

Introduction: Currently, there is no consensus on the indication of prophylactic surgery of the nodal compartments in the treatment of medullary thyroid carcinoma (MTC). The aim of our study was to perform a correlation study between preoperative calcitonin (basalCT) values and lymph node involvement to establish a criterion on which to base prophylactic surgery in these patients.

Material And Methods: We conducted an observational, retrospective and multicentre study with 29 hospitals. Read More

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Surgical aspects and controversies in the management of medullary thyroid cancer.

Ir J Med Sci 2022 Jan 22. Epub 2022 Jan 22.

Department of Otolaryngology, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland.

Medullary thyroid cancer (MTC) accounts for only 4% of thyroid carcinomas but 15% of thyroid cancer deaths. MTC is a tumour of the calcitonin secreting parafollicular C cells in the thyroid which can occur sporadically or be hereditary in multiple endocrine neoplasias type 2 syndromes due to germline RET mutations. Sporadic forms of MTC can also be caused by mutations in the RET protooncogene. Read More

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January 2022

Unusual increase in carcinoembryonic antigen despite response to selpercatinib in two patients with medullary thyroid cancer.

Eur Thyroid J 2022 02 4;11(2). Epub 2022 Feb 4.

Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Villejuif, France.

Introduction: Serum calcitonin (CT) and carcinoembryonic antigen (CEA) are valuable tumour markers in patients with medullary thyroid carcinoma (MTC). Both markers most often evolve in parallel after treatment. Selpercatinib (LOXO-292) is a highly selective RET kinase inhibitor indicated in advanced RET-mutant MTC patients. Read More

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February 2022