Medullary thyroid carcinoma: recent advances in identification, treatment, and prognosis

Bartz-Kurycki, Marisa A.; Oluwo, Omowunmi E.; Morris‐Wiseman, Lilah F.

doi:10.1177/20420188211049611

Cited by 23 publications

(15 citation statements)

References 80 publications

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“…A further problem, in addition to a more accurate classification, is the lack of specific markers for NEN diagnosis; Chromogranin A (CgA), synaptophysin (Syn), 5-Hydroxyindoleacetic Acid (5-HIAA), neuron-specific enolase (NSE) and cluster of differentiation 56 (CD56) (neural cell adhesion molecule) are currently used for GEP-NENs diagnosis [ 18 , 22 ] and Calcitonin for MTCs [ 23 ]. In GEP-NENs, both Syn and CgA are highly expressed in well-differentiated neoplasms, whereas poorly differentiated carcinomas often maintain synaptophysin positivity while losing CgA expression and acquiring NSE expression [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis

et al. 2022

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Background Neuroendocrine neoplasms (NENs) represent a heterogeneous class of rare tumors with increasing incidence. They are characterized by the ability to secrete peptide hormones and biogenic amines but other reliable biomarkers are lacking, making diagnosis and identification of the primary site very challenging. While in some NENs, such as the pancreatic ones, next generation sequencing technologies allowed the identification of new molecular hallmarks, our knowledge of the molecular profile of NENs from other anatomical sites is still poor. Methods Starting from the concept that NENs from different organs may be clinically and genetically correlated, we applied a multi-omics approach by combining multigene panel testing, CGH-array, transcriptome and miRNome profiling and computational analyses, with the aim to highlight common molecular and functional signatures of gastroenteropancreatic (GEP)-NENs and medullary thyroid carcinomas (MTCs) that could aid diagnosis, prognosis and therapy. Results By comparing genomic and transcriptional profiles, ATM-dependent signaling emerged among the most significant pathways at multiple levels, involving gene variations and miRNA-mediated regulation, thus representing a novel putative druggable pathway in these cancer types. Moreover, a set of circulating miRNAs was also selected as possible diagnostic/prognostic biomarkers useful for clinical management of NENs. Conclusions These findings depict a complex molecular and functional landscape of NENs, shedding light on novel therapeutic targets and disease biomarkers to be exploited.

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Section: Introductionmentioning

confidence: 99%

“…Equally, the prognostic role of 5-HIAA remains controversial [ 26 ]. For MTC diagnosis, calcitonin is a sensitive tumor marker because it correlates with C-cell mass and burden of the neoplasms [ 23 ], but this has also some limitations, such as inter-assay variability, concentration-dependent half-life and rapid degradation [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis

et al. 2022

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“…Targeted therapies are a management option for patients with progressive or symptomatic disease with locoregional or metastatic MTC [ 33 ]. Targeted therapies have helped supplant cytotoxic chemotherapy, which has low efficacy against disease progression, but there is still the problem of toxic side effects and frequent development of tumor resistance when using the current treatment regimen [ 92 ]. These problems indicate that there is still a need to develop an effective treatment for MTC.…”

Section: Systemic Treatmentmentioning

confidence: 99%

“…The registrational phase I/II ARROW trial, with the use of pralsetinib, in patients with MTC demonstrated rapid, potent and durable clinical activity, regardless of RET mutation (NCT03037385) [ 110 ]. These new RET-specific inhibitors have thus far shown a better side effect profile, which is probably due to their high selectivity with VEGFR bypass [ 92 ]. Previous generation of MKIs were not selective and were also blocking the VEGFR factor, part of the angiogenic and proliferative pathways.…”

Section: Systemic Treatmentmentioning

confidence: 99%

“…Previous generation of MKIs were not selective and were also blocking the VEGFR factor, part of the angiogenic and proliferative pathways. This caused intolerable sides effects, such as diarrhea, proteinuria, fatigue and hypertension [ 92 ]. Promisingly, when using selpercatinib in the LIBRETTO-001 study, researchers demonstrated a treatment-related adverse event that caused an overall drop-out rate in 2% of patients [ 109 ].…”

Section: Systemic Treatmentmentioning

confidence: 99%

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Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?

Kaliszewski

Ludwig

et al. 2022

Cancers

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Medullary thyroid carcinoma (MTC) is a neoplasm originating from parafollicular C cells. MTC is a rare disease, but its prognosis is less favorable than that of well-differentiated thyroid cancers. To improve the prognosis of patients with MTC, early diagnosis and prompt therapeutic management are crucial. In the following paper, recent advances in laboratory and imaging diagnostics and also pharmacological and surgical therapies of MTC are discussed. Currently, a thriving direction of development for laboratory diagnostics is immunohistochemistry. The primary imaging modality in the diagnosis of MTC is the ultrasound, but opportunities for development are seen primarily in nuclear medicine techniques. Surgical management is the primary method of treating MTCs. There are numerous publications concerning the stratification of particular lymph node compartments for removal. With the introduction of more effective methods of intraoperative parathyroid identification, the complication rate of surgical treatment may be reduced. The currently used pharmacotherapy is characterized by high toxicity. Moreover, the main limitation of current pharmacotherapy is the development of drug resistance. Currently, there is ongoing research on the use of tyrosine kinase inhibitors (TKIs), highly specific RET inhibitors, radiotherapy and immunotherapy. These new therapies may improve the prognosis of patients with MTCs.

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In Vitro Effects of Boric Acid on Cell Cycle, Apoptosis, and miRNAs in Medullary Thyroid Cancer Cells

Yıldırım,

Seçme,

Dodurga

et al. 2024

Biol Trace Elem Res

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Medullary thyroid cancer (MTC) is a highly aggressive and chemotherapy-resistant cancer originating from the thyroid’s parafollicular C cells. Due to its resistance to conventional treatments, alternative therapies such as boric acid have been explored. Boric acid, a boron-based compound, has shown anticarcinogenic effects, positioning it as a potential treatment option for MTC. TT medullary thyroid carcinoma cell line (TT cells) and human thyroid fibroblast (HThF cells) were utilized for the cell culture experiments. Cell viability was assessed using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. Total RNA was extracted using Trizol reagent for gene expression and microRNA (miRNA) analysis via reverse transcription-polymerase chain reaction (RT-PCR). The extent of apoptosis induced by boric acid was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Colony formation assays were conducted to evaluate the impact of boric acid on the colony-forming ability of MTC cells. At 48 h, 50% inhibitory concentration (IC50) of boric acid was found to be 35 μM. Treatment with boric acid resulted in significant modulation of apoptosis-related genes and miRNAs, including increased expression of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), apoptotic protease activating factor 1 (APAF-1), Bcl-2-associated X protein (Bax), caspase-3, and caspase-9. In contrast, the expression of B cell lymphoma 2 (Bcl2), B cell lymphoma‐ extra-large (Bcl-xl), and microRNA-21 (miR-21), which are linked to the aggressiveness of MTC, was significantly reduced. The TUNEL assay indicated a 14% apoptosis rate, and there was a 67.9% reduction in colony formation, as shown by the colony formation assay. Our study suggests that boric acid may have anticancer activity in MTC by modulating apoptotic pathways. These findings suggest that boric acid could be a potential therapeutic agent for MTC and possibly for other malignancies with similar pathogenic mechanisms.

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Medullary thyroid carcinoma: recent advances in identification, treatment, and prognosis

Cited by 23 publications

References 80 publications

Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis

Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis

Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?

In Vitro Effects of Boric Acid on Cell Cycle, Apoptosis, and miRNAs in Medullary Thyroid Cancer Cells

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