1,765 results match your criteria Medullary Thyroid Cancer and RET

Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study.

Lancet Diabetes Endocrinol 2021 Jun 9. Epub 2021 Jun 9.

Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.

Background: Oncogenic alterations in RET represent important therapeutic targets in thyroid cancer. We aimed to assess the safety and antitumour activity of pralsetinib, a highly potent, selective RET inhibitor, in patients with RET-altered thyroid cancers.

Methods: ARROW, a phase 1/2, open-label study done in 13 countries across 71 sites in community and hospital settings, enrolled patients 18 years or older with RET-altered locally advanced or metastatic solid tumours, including RET-mutant medullary thyroid and RET fusion-positive thyroid cancers, and an Eastern Co-operative Oncology Group performance status of 0-2 (later limited to 0-1 in a protocol amendment). Read More

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Cabozantinib promotes erythroid differentiation in K562 erythroleukemia cells through global changes in gene expression and JNK activation.

Cancer Gene Ther 2021 Jun 11. Epub 2021 Jun 11.

Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.

Cabozantinib is a potent tyrosine kinase inhibitor with multiple targets including MET, VEGFR2, RET, KIT, and FLT3. Cabozantinib is widely used for the treatment of medullary thyroid cancer and renal cell carcinoma. We recently suggested cabozantinib as a potential therapeutic alternative for acute myeloid leukemia (AML) patients with FLT3-internal tandem duplication (FLT3-ITD). Read More

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How I treat medullary thyroid cancer.

ESMO Open 2021 Jun 3;6(3):100183. Epub 2021 Jun 3.

Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; European Neuroendocrine Tumor Scoiety (ENETS) Center of Excellence Vienna, Medical University of Vienna, Austria.

Medullary thyroid cancer (MTC) represents a rare neuroendocrine neoplasm originating from neoplastic C-cells in the thyroid gland. While localized disease is potentially curable with an optimized surgical approach, the number of relapses is high, and a considerable number of patients present with primary metastatic disease. Multidisciplinary management including standardized surveillance following surgery, but also early involvement of medical oncologists, is therefore important. Read More

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Multiple endocrine neoplasia 2A with RET mutation p.Cys611Tyr: A case report.

Medicine (Baltimore) 2021 Jun;100(22):e26230

Department of Endocrinology and Metabolism, Longgang District People's Hospital of Shenzhen, The Third Affiliated Hospital (Provisional) of The Chinese University of Hong Kong, Longgang central city, Shenzhen, Guangdong, P.R. China.

Rationale: Multiple endocrine neoplasia 2A (MEN2A) is a rare autosomal-dominant genetic syndrome, frequently misdiagnosed or neglected clinically, resulting in delayed therapy to patients.

Patient Concerns: A 47-year-old Chinese male patient underwent laparoscopic right adrenal tumorectomy, and postoperative pathology confirmed the tumor as pheochromocytoma (PHEO). He was readmitted to the department of endocrinology and metabolism due to constant increase in carcinoembryonic antigen (CEA) at 5 months after the operation. Read More

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FDA Approval Summary: Pralsetinib for the Treatment of Lung and Thyroid Cancers With Gene Mutations or Fusions.

Clin Cancer Res 2021 May 27. Epub 2021 May 27.

Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.

The FDA granted accelerated approval for pralsetinib on September 4, 2020 for non-small cell lung cancer (NSCLC) and December 1, 2020 for thyroid cancer, for: (i) adult patients with metastatic fusion-positive NSCLC, (ii) adult and pediatric patients ≥12 years of age with advanced or metastatic -mutant medullary thyroid cancer who require systemic therapy, and (iii) adult and pediatric patients ≥12 years of age with advanced or metastatic fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate). Approval was based on the results of a multicenter, open-label, multi-cohort clinical trial (ARROW, NCT03037385), demonstrating substantial overall response rates (ORR) and durable responses in patients with altered tumors. ORRs within the approved patient populations ranged from 57% [95% confidence interval (CI), 46-68] in patients with fusion-positive NSCLC previously treated with platinum chemotherapy to 89% (95% CI, 52-100) in patients with fusion-positive thyroid cancer, with response duration of at least 6 months in most responders. Read More

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Afirma Genomic Sequencing Classifier & Xpression Atlas Molecular Findings in Consecutive Bethesda III-VI Thyroid Nodules.

J Clin Endocrinol Metab 2021 May 19. Epub 2021 May 19.

Department of Medical Affairs, Veracyte, Inc., South San Francisco, California.

Context: Broad genomic analyses among thyroid histologies have been described from relatively small cohorts.

Objective: Investigate the molecular findings across a large, real-world cohort of thyroid fine needle aspiration (FNA) samples.

Design: Retrospective analysis of RNA sequencing data files. Read More

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Persistence of Elevated Procalcitonin in a Patient with Covid-19 Uncovering a Diagnosis of Medullary Thyroid Carcinoma.

AACE Clin Case Rep 2021 May 12. Epub 2021 May 12.

Objectives: During this ongoing pandemic of coronavirus disease 2019 (COVID-19), procalcitonin (PCT) assay has proven to be a useful tool in assisting clinicians to diagnose bacterial superinfection. However, in the absence of signs of infection or at resolution thereof, inappropriately and persistently high PCT may suggest and reveal the presence of other pathologies We report a patient with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia in whom persistence of initially elevated PCT during recovery prompted the diagnosis of medullary thyroid cancer (MTC).

Case Report: A 43- year-old man presented with a two-day history of fever, sneezing, sore throat and dry cough. Read More

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Crude annual incidence rate of medullary thyroid cancer and RET mutation frequency.

Croat Med J 2021 Apr;62(2):110-119

Barbara Perić, Department of Surgical Oncology, Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana, Slovenia,

Aim: To determine the frequency and type of RET mutation in Slovenian medullary thyroid cancer (MTC) patients and estimate the crude annual incidence of MTC in Slovenia.

Methods: This referral-center retrospective analysis involved 186 MTC patients diagnosed between 1995 and 2015 and their relatives who underwent genetic counseling and testing. The crude incidence rate of MTC was estimated with the joinpoint regression analysis. Read More

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Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib.

Int J Mol Sci 2021 Apr 20;22(8). Epub 2021 Apr 20.

Department of Biochemistry, Faculty of Science, Charles University, Albertov 6, 128 00 Prague 2, Czech Republic.

A tyrosine kinase inhibitor, vandetanib (Van), is an anticancer drug affecting the signaling of VEGFR, EGFR and RET protooncogenes. Van is primarily used for the treatment of advanced or metastatic medullary thyroid cancer; however, its usage is significantly limited by side effects, particularly cardiotoxicity. One approach to minimize them is the encapsulation or binding of Van in- or onto a suitable carrier, allowing targeted delivery to tumor tissue. Read More

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Occurrence of sporadic medullary thyroid carcinoma in Graves' disease in association with a RET proto-oncogene mutation.

Acta Clin Belg 2021 Apr 29:1-4. Epub 2021 Apr 29.

Unit of Digestive, Endocrine and General Surgery, Department of Surgery, Université Catholique de Louvain, Yvoir, Belgium.

: Graves' disease may be associated with thyroid cancer, particularly differentiated thyroid cancer. Medullary thyroid cancer (MTC) is less common. The occurrence of sporadic MTC in Graves' disease in the presence of a RET proto-oncogene has never been reported. Read More

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Case Report: Next-Generation Sequencing Reveals Tumor Origin in a Female Patient With Brain Metastases.

Front Oncol 2021 12;11:569429. Epub 2021 Apr 12.

Neurosurgery department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Brain metastasis mainly originates from lung cancer. Napsin A and TTF-1 factors have frequently been detected in lung adenocarcinoma cases. Brain metastasis tumors with napsin A and TTF-1 positive are easily classified as lung adenocarcinoma origin. Read More

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Spectrum of Germline RET variants identified by targeted sequencing and associated Multiple Endocrine Neoplasia type 2 susceptibility in China.

BMC Cancer 2021 Apr 7;21(1):369. Epub 2021 Apr 7.

Department of Oncologic and Urologic Surgery, The 903rd PLA Hospital, Wenzhou Medical University, 40 Jichang Road, Hangzhou, 310004, Zhejiang Province, China.

Background: Germline RET mutations and variants are involved in development of multiple endocrine neoplasia type 2 (MEN2). The present study investigated a spectrum of RET variants, analyzed genotype-phenotype relationships, and evaluated their effect on the MEN2 phenotype in Han Chinese patients.

Methods: Targeted sequencing detected germline RET variants in 697 individuals, including 245 MEN2, 120 sporadic medullary thyroid cancer (MTC), and 15 pheochromocytoma (PHEO) patients and their 493 relatives. Read More

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Medullary thyroid cancer: molecular factors, management and treatment.

Rom J Morphol Embryol 2020 Jul-Sep;61(3):681-686

3rd Department of Surgery, AHEPA University Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece;

Medullary thyroid cancer (MTC) is an infrequent neuroendocrine tumor, which amounts to 3-5% of all thyroid malignancies. Approximately 75-80% of MTCs are sporadic neoplasms. The rest of 20-25% are familial cases that belong to multiple endocrine neoplasia (MEN) syndromes, specifically MEN2 and MEN3. Read More

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Multiple endocrine neoplasia type 2: A reveiw.

Semin Cancer Biol 2021 Apr 1. Epub 2021 Apr 1.

Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Health Sciences, Copenhagen University, Copenhagen, Denmark. Electronic address:

Multiple endocrine neoplasias are rare hereditary syndromes some of them with malignant potential. Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome due to germline variants in the REarranged during Transfection (RET) proto-oncogene. There are two distinct clinical entities: MEN 2A and MEN 2B. Read More

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Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model.

Int J Mol Sci 2021 Mar 16;22(6). Epub 2021 Mar 16.

Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano, IRCCS, 20095 Cusano Milanino, MI, Italy.

Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. Read More

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Exceptionality of Distant Metastases in Node-Negative Hereditary and Sporadic Medullary Thyroid Cancer: Lessons Learned.

J Clin Endocrinol Metab 2021 Mar 31. Epub 2021 Mar 31.

Department of Visceral, Vascular and Endocrine Surgery, Section of Endocrine Surgery, University of Duisburg-Essen, Hufelandstraße, Essen, Germany.

Context: Risk factors of lymph node and distant metastases have rarely been analyzed in hereditary and sporadic medullary thyroid cancer (MTC) using large genetic-clinical data sets.

Objective: This comprehensive investigation aimed to explore risk factors of lymph node and distant metastases and interdependencies between age at thyroidectomy, primary tumor size, lymph node metastasis and distant metastasis in patients with hereditary and sporadic MTC.

Methods: Comparative analyses of risk factors of metastasis, stratified by hereditary MTC (four mutational risk categories) and sporadic MTC. Read More

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Evaluation of grade in a genotyped cohort of sporadic medullary thyroid carcinomas.

Histopathology 2021 Mar 24. Epub 2021 Mar 24.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Aims: Tumour grade and RET mutation status, especially the presence of high-risk exon 15 and 16 RET mutations, have been reported to be prognostic in patients with sporadic medullary thyroid carcinoma (MTC). The aims of our study were to evaluate the performance of two recently proposed grading systems and to assess the association between grade and genotype in a cohort of sporadic MTCs.

Methods And Results: We identified 44 sporadic MTCs. Read More

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DLL3 (delta-like protein 3) expression correlates with stromal desmoplasia and lymph node metastases in medullary thyroid carcinomas.

Endocr Connect 2021 Mar;10(3):283-289

Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.

Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbor somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Read More

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Case report of adrenocortical carcinoma associated with double germline mutations in MSH2 and RET.

Am J Med Genet A 2021 04 21;185(4):1282-1287. Epub 2021 Feb 21.

Developmental Therapeutics Branch, National Cancer Institute, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.

Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that originates in the outer layer of the adrenal gland. Most ACCs are sporadic, but a small percentage of cases are due to hereditary cancer syndromes such as Li-Fraumeni syndrome (LFS), Lynch syndrome (LS), and familial adenomatous polyposis (FAP). Multiple endocrine neoplasia type 2A (MEN2A) is an inherited disorder that predisposes to medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia. Read More

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The importance of the RET gene in thyroid cancer and therapeutic implications.

Nat Rev Endocrinol 2021 05 18;17(5):296-306. Epub 2021 Feb 18.

Département de Médecine Nucléaire et Cancérologie Endocrinienne, Gustave Roussy, Université Paris-Saclay, Villejuif, France.

Since the discovery of the RET receptor tyrosine kinase in 1985, alterations of this protein have been found in diverse thyroid cancer subtypes. RET gene rearrangements are observed in papillary thyroid carcinoma, which result in RET fusion products. By contrast, single amino acid substitutions and small insertions and/or deletions are typical of hereditary and sporadic medullary thyroid carcinoma. Read More

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Lenvatinib as a salvage therapy for advanced metastatic medullary thyroid cancer.

J Endocrinol Invest 2021 Feb 17. Epub 2021 Feb 17.

Department of Clinical and Experimental Medicine, Unit of Endocrinology, Pisa University Hospital, Via Paradisa 2, 56124, Pisa, Italy.

Purpose: Patients with advanced progressive metastatic medullary thyroid cancer (MTC), show poor prognosis and few available systemic therapeutic options. After the loss of clinical benefit with other tyrosine kinase inhibitors (TKI), we evaluated the use of lenvatinib as salvage therapy.

Methods: Ten patients who experienced the loss of clinical benefit after treatment with at least one previous TKI, were treated with lenvatinib. Read More

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February 2021

A Narrative Review of Genetic Alterations in Primary Thyroid Epithelial Cancer.

Int J Mol Sci 2021 Feb 9;22(4). Epub 2021 Feb 9.

Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, 56124 Pisa, Italy.

Thyroid carcinoma is the most frequent endocrine neoplasia. Different types of thyroid carcinoma are described: well-differentiated papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinoma (PDTC), follicular thyroid carcinoma (FTC), anaplastic thyroid carcinoma (ATC), and medullary thyroid carcinoma (MTC). MTC is inherited as an autosomal dominant trait in 25% of cases. Read More

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February 2021

Perspectives on the Treatment of Advanced Thyroid Cancer: Approved Therapies, Resistance Mechanisms, and Future Directions.

Front Oncol 2020 25;10:592202. Epub 2021 Jan 25.

Division of Hematology/Oncology, Department of Medicine, Los Angeles, CA, United States.

For differentiated thyroid cancer (DTC), systemic therapy with radioactive iodine (RAI) is utilized for radiosensitive disease, while for radioiodine refractory (RAIR) disease, current standard of care is treatment with multikinase tyrosine kinase inhibitors (TKI). For BRAF-mutant DTC or anaplastic thyroid cancer (ATC), treatment with inhibitors targeting BRAF and MEK are important advances. RET-inhibitors for RET-mutated medullary thyroid cancer (MTC) recently have been FDA-approved for metastatic disease. Read More

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January 2021

Late diagnosis of metastatic pheochromocytoma in multiple endocrine neoplasia 2B with rapid clinical decline.

BMJ Case Rep 2021 Feb 4;14(2). Epub 2021 Feb 4.

Hematology/Oncology, UF Health Cancer Center-Orlando Health, Orlando, Florida, USA.

Multiple endocrine neoplasia type 2B (MEN2B) is the rarest and most aggressive of the MEN syndromes. It is characterised by medullary thyroid cancer (MTC), pheochromocytoma, marfanoid body habitus, mucosal neuromas and colonic dysfunction. Patients typically present with chronic constipation and MTC in early childhood. Read More

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February 2021

ONC201 Shows Potent Anticancer Activity Against Medullary Thyroid Cancer via Transcriptional Inhibition of , , and .

Mol Cancer Ther 2021 04 3;20(4):665-675. Epub 2021 Feb 3.

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

Gain-of-function point mutations in the receptor tyrosine kinase , a driver oncogene in medullary thyroid carcinoma (MTC), prevent apoptosis through inhibition of ATF4, a critical transcriptional regulator of endoplasmic reticulum stress. However, the critical regulatory mechanisms driving RET-dependent oncogenesis remain elusive, and there is a clinical need to identify a transcriptional RET inhibitor. Here, we found that RET depletion decreased and mRNA and protein expression in MTC cells. Read More

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Molecular Modelling Studies on Pyrazole Derivatives for the Design of Potent Rearranged during Transfection Kinase Inhibitors.

Molecules 2021 Jan 28;26(3). Epub 2021 Jan 28.

Department of Biomedical Sciences, College of Medicine, Chosun University, Gwangju 501-759, Korea.

RET (rearranged during transfection) kinase, one of the receptor tyrosine kinases, plays a crucial role in the development of the human nervous system. It is also involved in various cell signaling networks responsible for the normal cell division, growth, migration, and survival. Previously reported clinical studies revealed that deregulation or aberrant activation of RET signaling can cause several types of human cancer. Read More

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January 2021

Genomics and Epigenomics of Medullary Thyroid Carcinoma: From Sporadic Disease to Familial Manifestations.

Endocr Pathol 2021 Mar 25;32(1):35-43. Epub 2021 Jan 25.

Massachusetts General Hospital, Boston, USA.

Our understanding of the genomics and epigenomics of medullary thyroid carcinoma (MTC) has advanced since the initial recognition of RET as a driver of MTC tumorigenesis in familial MTC. We now have insight into the frequency and prognostic significance of specific RET mutations in sporadic MTC. For example, the most common RET mutation in sporadic MTC is the RET Met918Thr mutation, the same mutation that underlies MEN2B and a poor prognosticator. Read More

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RET mutated C-cells proliferate more rapidly than non-mutated neoplastic cells.

Endocr Connect 2021 Feb;10(2):124-130

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

A statistically significant higher prevalence of the RET p.Met918Thr somatic mutation, identified by direct sequencing, was previously reported in MTC > 2 cm than in smaller tumors. Aim of this study was to correlate the full RET and RAS mutation profile, identified by a Next Generation Sequencing approach, with the growth rate, proliferation and tumor size of MTC. Read More

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February 2021

Antineoplastic Activity of an Old Natural Antidiabetic Biguanoid on the Human Thyroid Carcinoma Cell Line.

Anticancer Agents Med Chem 2021 Jan 17. Epub 2021 Jan 17.

Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran. Iran.

Background: In the last decades, metformin (Met), an herbal anti-diabetic medicine, has been proposed as an anti-cancer agent.

Objective: Thyroid cancers are the most common malignancy of the endocrine system. Therefore, the current study was performed to assess the effects of Met on cell proliferation and activation of the Phosphoinositide 3-Kinase (PI3K)/Protein kinase B (AKT)/Forkhead Box O1 (FOXO1) signaling pathway in the Medullary Thyroid Carcinoma (MTC) cells. Read More

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January 2021

Characterization of LDD-2633 as a Novel RET Kinase Inhibitor with Anti-Tumor Effects in Thyroid Cancer.

Pharmaceuticals (Basel) 2021 Jan 6;14(1). Epub 2021 Jan 6.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju-si 52828, Korea.

Rearranged during transfection (RET), a receptor tyrosine kinase, is activated by glial cell line-derived neurotrophic factor family ligands. Chromosomal rearrangement or point mutations in are observed in patients with papillary thyroid and medullary thyroid carcinomas. Oncogenic alteration of results in constitutive activation of RET activity. Read More

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January 2021