RARE DISEASE
Anaplastic thyroid carcinoma
Anaplastic thyroid carcinoma
Anaplastic thyroid carcinoma
Drug discovery
6
drugs
With orphan designations
Overview
Anaplastic thyroid carcinoma (ATC) is a rare, undifferentiated malignancy representing 1-2% of thyroid cancers but responsible for 14-50% of thyroid cancer-related deaths [5][12][19]. Characterized by rapid growth (weeks), local invasion, and early metastasis, it has a dismal median survival of 3-9 months [5][16]. All cases are classified as stage IV at diagnosis [7]. Treatment requires aggressive multimodal approaches, including surgery (when feasible), radiotherapy, chemotherapy, and emerging targeted therapies [3][8][18].
Categories: rare endocrine diseases, rare neoplastic diseases
Research Papers
2,252 drug discovery papers about Anaplastic thyroid carcinoma, with 7 first-in-class and 10 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,252 drug discovery papers about Anaplastic thyroid carcinoma, with 7 first-in-class and 10 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Signaling pathways and targeted therapy in high‑risk refractory thyroid cancer: From bench to bedside (Review).
Thyroid cancer is the most common endocrine malignancy worldwide, with its incidence increasing markedly over the past several decades, while mortality trends have shown complex patterns. High‑risk refractory thyroid cancers (including radioactive iodine‑refractory differentiated thyroid cancer, poorly differentiated thyroid cancer, anaplastic thyroid carcinoma, progressive medullary thyroid carcinoma and locally advanced disease) pose major challenges in clinical management. The present review systematically reviewed recent epidemiological trends in thyroid cancer and provided an in‑depth exploration of the molecular regulatory mechanisms of key signaling pathways, including MAPK, PI3K/AKT, Janus kinase/STAT, WNT/β‑catenin and NF‑κB, along with their roles in the pathogenesis and progression of thyroid cancer. Based on this, the latest clinical research advances in targeted therapies for high‑risk, refractory thyroid cancer are elaborated on, covering multikinase inhibitors, B‑Raf proto‑oncogene, serine/threonine kinase/mitogen‑activated protein kinase kinase inhibitors, immunotherapy combinations, innovative targeted strategies and redifferentiation approaches. Finally, future directions are discussed based on the 'total treatment' paradigm and strategies to overcome drug resistance, aiming to provide a systematic reference for basic research and clinical translation in thyroid cancer.
2026-08-13 | Thyroid Cancer: From Potential Drivers to Real Modulators.
The advent of cancer immunotherapy opened a transformative era in oncology, shifting the focus from targeting mutated genes through precision oncology to harnessing the body's immune system via agnostic therapies. This paradigm has demonstrated that a deeper understanding of the tumor immune microenvironment (TIME) can transcend the challenges posed by cancer's genetic diversity and evolutionary dynamics. In the case of thyroid cancer, progress in immunotherapy has been comparatively slow. Much of the current research still centers on the genetic landscape of thyroid tumors rather than on comprehensive exploration of their TIME. The TIME, composed of immune cells such as macrophages, lymphocytes, natural killer cells, and mast cells, along with a network of signaling molecules, evolves alongside tumor growth and metastasis. It both influences and is influenced by genetic alterations, metabolic conditions, and therapeutic interventions. This dynamic crosstalk defines the clinical and biological heterogeneity of thyroid cancers; from the aggressive anaplastic thyroid carcinoma (ATC) to the more indolent papillary thyroid carcinoma (PTC). Mapping the spatial and temporal changes within the TIME offers the opportunity to design therapies that counter immune evasion and enhance treatment response. As understanding of the tumor microenvironment deepens, thyroid cancer therapy is undergoing a major shift; from strategies aimed merely at genetic mutations to integrated, combinational approaches incorporating personalized immunotherapy. Building on recent findings, which detail immune cell composition and therapeutic implications in thyroid malignancies, this review expands on the molecular and cellular mechanisms shaping the microenvironment. We highlight how oncogenic signaling, stromal remodeling, and metabolic reprogramming coordinate to influence tumor immunity, and we explore emerging strategies that aim to reengineer the tumor microenvironment for improved therapeutic outcomes.
2026-08-08 | Single-cohort next-generation sequencing analysis of 713 anaplastic thyroid carcinomas: unreported gene alterations and actionable targets.
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal thyroid malignancies, with limited effective treatment options. We aimed to identify previously unreported gene alterations and evaluate the potential for clinically actionable targeted therapies in ATC using the largest single next-generation sequencing (NGS) cohort to date. This retrospective genomic analysis included deidentified NGS data from 713 patients with ATC obtained from the FoundationCORE database. Pathogenic gene alterations were analyzed for frequency. A comprehensive review of the literature and genomic databases was performed to identify alterations not previously reported in ATC and to assess associated targeted therapies. Targeted sequencing of 713 ATC tumor specimens identified 250 genes with pathogenic or likely pathogenic alterations, including 108 not previously reported in ATC. Among these novel genes, 24 were altered in 5 or more cases, with MTAP (methylthioadenosine phosphorylase) showing the highest frequency (15.26%). MTAP was also co-deleted with CDKN2A/B at significantly higher rates than previously reported. Notably, 99.58% of cases harbored at least 1 gene alteration associated with a potentially actionable therapy. Among the 250 altered genes, 150 (60.0%) had at least 1 available corresponding targeted therapy, and 75.0% of drug categories demonstrated multiple-gene targeting capabilities. This largest single-cohort NGS data analysis identified 108 previously unreported genomic alterations in ATC, significantly expanding the understanding of the genomic landscape of this aggressive cancer. Moreover, these findings highlight a broad range of potentially actionable alterations and underscore the importance of identifying driver mutations and combination therapeutic strategies.
2026-08-06 | Updates in systemic therapy for refractory thyroid carcinoma - targeted agents, immunotherapy, and chemotherapy.
Systemic therapy for refractory thyroid carcinoma has moved from chemotherapy and broad multikinase inhibitors towards molecularly targeted treatment. This review summarizes recent practice-changing developments in radioiodine-refractory differentiated thyroid carcinoma, with brief updates on medullary and anaplastic thyroid carcinoma. Recent guidelines and clinical studies emphasize early molecular testing, and careful selection of patients for personalized systemic therapy. Lenvatinib remains the preferred first-line multikinase inhibitor for most progressive radioiodine-refractory differentiated thyroid cancers without actionable alterations, while cabozantinib is the best-supported option after lenvatinib. Selective Rearranged during transfection (RET), Neurotrophic Tropomyosin Receptor Kinase (NTRK), and Anaplastic Lymphoma Kinase (ALK) inhibitors have reshaped treatment for fusion-positive disease, and MAPK inhibition can restore radioiodine avidity in selected tumours. In anaplastic thyroid carcinoma, BRAF/MEK-directed treatment and emerging immunotherapy-targeted therapy combinations have prolonged survival and in select instances also enabled resection. Contemporary management of refractory thyroid carcinoma relies heavily on early molecular testing and utilizing genotype-directed targeted therapy options.
2026-08-05 | CENPM as a biomarker and therapeutic target for lymph node metastasis in thyroid carcinoma.
Lymph node metastasis (LNM) is a key prognostic determinant in thyroid carcinoma (THCA), yet molecular markers capturing intrinsic metastatic potential are limited. Generalized additive models were applied to TCGA-THCA data to screen for genes with diametrically opposite expression-tumor diameter relationships between N0 and N1 patients. CENPM was subsequently validated in independent transcriptomic cohorts, spatial transcriptomics, and immunohistochemistry. Single-cell transcriptomics, in silico knockout, drug repositioning, and molecular docking were employed to dissect its immunological roles and therapeutic relevance. CENPM expression increased with tumor diameter in N0 but decreased in N1, and high CENPM was associated with poorer disease-free survival. CENPM was predominantly enriched in CD8+ naïve and effector T cells, particularly in anaplastic carcinoma. Virtual knockout predicted downstream transcriptional changes associated with lymphocyte activation, translational machinery, and immune effector pathways. Drug repositioning identified filgotinib as a candidate to reverse the CENPM-high signature, with stable CENPM-filgotinib binding confirmed by docking and molecular dynamics. CENPM shows diametrically opposite expression-diameter relationships between N0 and N1 patients, suggesting a shift in biological behavior upon nodal involvement, with potential therapeutic relevance.
2026-08-14 | Signaling pathways and targeted therapy in high‑risk refractory thyroid cancer: From bench to bedside (Review).
Thyroid cancer is the most common endocrine malignancy worldwide, with its incidence increasing markedly over the past several decades, while mortality trends have shown complex patterns. High‑risk refractory thyroid cancers (including radioactive iodine‑refractory differentiated thyroid cancer, poorly differentiated thyroid cancer, anaplastic thyroid carcinoma, progressive medullary thyroid carcinoma and locally advanced disease) pose major challenges in clinical management. The present review systematically reviewed recent epidemiological trends in thyroid cancer and provided an in‑depth exploration of the molecular regulatory mechanisms of key signaling pathways, including MAPK, PI3K/AKT, Janus kinase/STAT, WNT/β‑catenin and NF‑κB, along with their roles in the pathogenesis and progression of thyroid cancer. Based on this, the latest clinical research advances in targeted therapies for high‑risk, refractory thyroid cancer are elaborated on, covering multikinase inhibitors, B‑Raf proto‑oncogene, serine/threonine kinase/mitogen‑activated protein kinase kinase inhibitors, immunotherapy combinations, innovative targeted strategies and redifferentiation approaches. Finally, future directions are discussed based on the 'total treatment' paradigm and strategies to overcome drug resistance, aiming to provide a systematic reference for basic research and clinical translation in thyroid cancer.
2026-08-13 | Thyroid Cancer: From Potential Drivers to Real Modulators.
The advent of cancer immunotherapy opened a transformative era in oncology, shifting the focus from targeting mutated genes through precision oncology to harnessing the body's immune system via agnostic therapies. This paradigm has demonstrated that a deeper understanding of the tumor immune microenvironment (TIME) can transcend the challenges posed by cancer's genetic diversity and evolutionary dynamics. In the case of thyroid cancer, progress in immunotherapy has been comparatively slow. Much of the current research still centers on the genetic landscape of thyroid tumors rather than on comprehensive exploration of their TIME. The TIME, composed of immune cells such as macrophages, lymphocytes, natural killer cells, and mast cells, along with a network of signaling molecules, evolves alongside tumor growth and metastasis. It both influences and is influenced by genetic alterations, metabolic conditions, and therapeutic interventions. This dynamic crosstalk defines the clinical and biological heterogeneity of thyroid cancers; from the aggressive anaplastic thyroid carcinoma (ATC) to the more indolent papillary thyroid carcinoma (PTC). Mapping the spatial and temporal changes within the TIME offers the opportunity to design therapies that counter immune evasion and enhance treatment response. As understanding of the tumor microenvironment deepens, thyroid cancer therapy is undergoing a major shift; from strategies aimed merely at genetic mutations to integrated, combinational approaches incorporating personalized immunotherapy. Building on recent findings, which detail immune cell composition and therapeutic implications in thyroid malignancies, this review expands on the molecular and cellular mechanisms shaping the microenvironment. We highlight how oncogenic signaling, stromal remodeling, and metabolic reprogramming coordinate to influence tumor immunity, and we explore emerging strategies that aim to reengineer the tumor microenvironment for improved therapeutic outcomes.
2026-08-08 | Single-cohort next-generation sequencing analysis of 713 anaplastic thyroid carcinomas: unreported gene alterations and actionable targets.
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal thyroid malignancies, with limited effective treatment options. We aimed to identify previously unreported gene alterations and evaluate the potential for clinically actionable targeted therapies in ATC using the largest single next-generation sequencing (NGS) cohort to date. This retrospective genomic analysis included deidentified NGS data from 713 patients with ATC obtained from the FoundationCORE database. Pathogenic gene alterations were analyzed for frequency. A comprehensive review of the literature and genomic databases was performed to identify alterations not previously reported in ATC and to assess associated targeted therapies. Targeted sequencing of 713 ATC tumor specimens identified 250 genes with pathogenic or likely pathogenic alterations, including 108 not previously reported in ATC. Among these novel genes, 24 were altered in 5 or more cases, with MTAP (methylthioadenosine phosphorylase) showing the highest frequency (15.26%). MTAP was also co-deleted with CDKN2A/B at significantly higher rates than previously reported. Notably, 99.58% of cases harbored at least 1 gene alteration associated with a potentially actionable therapy. Among the 250 altered genes, 150 (60.0%) had at least 1 available corresponding targeted therapy, and 75.0% of drug categories demonstrated multiple-gene targeting capabilities. This largest single-cohort NGS data analysis identified 108 previously unreported genomic alterations in ATC, significantly expanding the understanding of the genomic landscape of this aggressive cancer. Moreover, these findings highlight a broad range of potentially actionable alterations and underscore the importance of identifying driver mutations and combination therapeutic strategies.
2026-08-06 | Updates in systemic therapy for refractory thyroid carcinoma - targeted agents, immunotherapy, and chemotherapy.
Systemic therapy for refractory thyroid carcinoma has moved from chemotherapy and broad multikinase inhibitors towards molecularly targeted treatment. This review summarizes recent practice-changing developments in radioiodine-refractory differentiated thyroid carcinoma, with brief updates on medullary and anaplastic thyroid carcinoma. Recent guidelines and clinical studies emphasize early molecular testing, and careful selection of patients for personalized systemic therapy. Lenvatinib remains the preferred first-line multikinase inhibitor for most progressive radioiodine-refractory differentiated thyroid cancers without actionable alterations, while cabozantinib is the best-supported option after lenvatinib. Selective Rearranged during transfection (RET), Neurotrophic Tropomyosin Receptor Kinase (NTRK), and Anaplastic Lymphoma Kinase (ALK) inhibitors have reshaped treatment for fusion-positive disease, and MAPK inhibition can restore radioiodine avidity in selected tumours. In anaplastic thyroid carcinoma, BRAF/MEK-directed treatment and emerging immunotherapy-targeted therapy combinations have prolonged survival and in select instances also enabled resection. Contemporary management of refractory thyroid carcinoma relies heavily on early molecular testing and utilizing genotype-directed targeted therapy options.
2026-08-05 | CENPM as a biomarker and therapeutic target for lymph node metastasis in thyroid carcinoma.
Lymph node metastasis (LNM) is a key prognostic determinant in thyroid carcinoma (THCA), yet molecular markers capturing intrinsic metastatic potential are limited. Generalized additive models were applied to TCGA-THCA data to screen for genes with diametrically opposite expression-tumor diameter relationships between N0 and N1 patients. CENPM was subsequently validated in independent transcriptomic cohorts, spatial transcriptomics, and immunohistochemistry. Single-cell transcriptomics, in silico knockout, drug repositioning, and molecular docking were employed to dissect its immunological roles and therapeutic relevance. CENPM expression increased with tumor diameter in N0 but decreased in N1, and high CENPM was associated with poorer disease-free survival. CENPM was predominantly enriched in CD8+ naïve and effector T cells, particularly in anaplastic carcinoma. Virtual knockout predicted downstream transcriptional changes associated with lymphocyte activation, translational machinery, and immune effector pathways. Drug repositioning identified filgotinib as a candidate to reverse the CENPM-high signature, with stable CENPM-filgotinib binding confirmed by docking and molecular dynamics. CENPM shows diametrically opposite expression-diameter relationships between N0 and N1 patients, suggesting a shift in biological behavior upon nodal involvement, with potential therapeutic relevance.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
6 orphan drug designations for Anaplastic thyroid carcinoma, including 4 approved therapies.
6 orphan drug designations for Anaplastic thyroid carcinoma, including 4 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
pralsetinib [Gavreto] | small molecules | FDA | 2020-05-26 | 2020-12-01 | Rigel Pharmaceuticals, Inc. |
autologous chimeric antigen receptor (CAR) T cells targeting intercellular adhesion molecule-1 (ICAM-1) | cell therapies | FDA | 2019-04-09 | — | AffyImmune Therapeutics, Inc. |
dabrafenib and trametinib [Tafinlar(r) Capsules a nd Mekinist(r) Tablets] | small molecules | FDA | 2016-09-01 | 2018-05-04 | Novartis Pharmaceuticals Corporation |
vemurafenib | small molecules | FDA | 2013-11-26 | — | Genentech, Inc. |
cabozantinib [Cometriq] | small molecules | FDA | 2010-11-29 | 2012-11-29 | Exelixis, Inc. |
vandetanib [CAPRELSA(r)] | small molecules | FDA | 2005-10-21 | 2011-04-06 | Genzyme Corporation |
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