☆ 4.6 Review

NTRK fusions in thyroid cancer: Pathology and clinical aspects

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY (2023)

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Article Oncology

NTRK-rearranged papillary thyroid carcinoma demonstrates frequent subtle nuclear features and indeterminate cytologic diagnoses

Yu-Cheng Lee et al.

Summary: NTRK-rearranged PTCs exhibit intermediate nuclear features, such as subtle nuclear grooving, infrequent nuclear elongation, and rare pseudoinclusions, leading to a significantly higher rate of TBS III-IV diagnoses compared to other molecular alterations in PTC.

CANCER CYTOPATHOLOGY (2022)

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Article Oncology

Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors

George D. Demetri et al.

Summary: This study provides additional evidence on the safety and efficacy of Entrectinib in treating NTRK fusion-positive solid tumors, with prolonged follow-up and an increased number of patients.

CLINICAL CANCER RESEARCH (2022)

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Article Oncology

Leveraging artificial intelligence to predict ERG gene fusion status in prostate cancer

Vipulkumar Dadhania et al.

Summary: A deep learning-based algorithm has been developed to identify ERG rearrangement status in prostatic adenocarcinoma based on digitized slides of H&E morphology alone. The model successfully predicts ERG rearrangement status in the majority of prostatic adenocarcinomas, eliminating the need for ancillary studies to assess for ERG gene rearrangement in prostate cancer.

BMC CANCER (2022)

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Review Oncology

Liquid biopsies to monitor and direct cancer treatment in colorectal cancer

Gianluca Mauri et al.

Summary: Colorectal cancer is a prevalent and deadly cancer, and there is a clinical need for better patient selection for systemic treatments. Genotyping circulating tumour DNA is a potential method to personalize treatment and overcome limitations of traditional biopsy approaches. This review summarizes the evidence of ctDNA applicability in colorectal cancer and discusses ongoing clinical trials.

BRITISH JOURNAL OF CANCER (2022)

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Article Endocrinology & Metabolism

Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma

Steven G. Waguespack et al.

Summary: This study evaluated the efficacy and safety of Larotrectinib in patients with TRK fusion-positive thyroid carcinoma. The results showed that Larotrectinib demonstrated rapid and durable disease control and a favorable safety profile in these patients, making it a potential treatment option for advanced thyroid carcinoma.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2022)

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Article Pathology

Detection of NTRK fusions in glioblastoma: fluorescent in situ hybridisation is more useful than pan-TRK immunohistochemistry as a screening tool prior to RNA sequencing

Amelie Bourhis et al.

Summary: This study evaluated efficient diagnostic tools and strategies for identifying rare NTRK rearrangements in glioblastomas. Through FISH and RNA sequencing analyses, several cases of NTRK-rearranged glioblastomas were identified, and appropriate immunostaining criteria were proposed to distinguish between NTRK-rearranged and non-NTRK-rearranged gliomas.

PATHOLOGY (2022)

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Review Medicine, General & Internal

A review of NTRK fusions in cancer

Cristina Alexandra Manea et al.

Summary: The NTRK family, responsible for neuronal development, consists of receptor proteins encoded by the NTRK1, NTRK2, and NTRK3 genes. Alterations in NTRK genes can lead to carcinogenesis in both neurogenic and non-neurogenic cells. Although NTRK gene fusion is rare in solid tumors (<1%), it is highly prevalent in rare tumors. The presence of NTRK1 gene fusion is associated with favorable prognosis in certain types of neoplasia, while the presence of NTRK2 may indicate a poor prognosis. Identification of cancer patients with NTRK gene fusions has increased with the development of NTRK inhibitors, providing promising opportunities for personalized therapeutics.

ANNALS OF MEDICINE AND SURGERY (2022)

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Review Biochemistry & Molecular Biology

Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer

Ana Julia Aguiar de Freitas et al.

Summary: Liquid biopsy is a new technique that can assess the molecular heterogeneity of breast cancer, aiding in personalized treatment, early screening, and accurate diagnosis. By sampling tumor components from biological samples such as blood, this method can detect circulating tumor cells, circulating tumor DNA, and other markers, providing guidance for breast cancer therapy.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Oncology

Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer

Peilong Li et al.

Summary: Lung cancer is the leading cause of cancer-related deaths, with poor prognosis due to late-stage diagnosis. DNA methylation, a widely studied epigenetic modification, plays a crucial role in early tumorigenesis. Liquid biopsy has rapidly developed and shows promise for early detection of lung cancer based on DNA methylation.

CLINICAL EPIGENETICS (2022)

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Letter Endocrinology & Metabolism

Ultrasensitive detection of BRAF V600E mutations in circulating tumor DNA of patients with metastatic thyroid cancer

Mohamed A. Gouda et al.

ENDOCRINE (2022)

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Review Pharmacology & Pharmacy

Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers

Tingting Jiang et al.

Summary: TRKA, TRKB, and TRKC are important members of the cell surface receptor tyrosine kinase family, regulating cell proliferation, differentiation, and apoptosis. NTRK gene fusions act as oncogenic drivers for a variety of tumors, making TRK inhibitors promising targets for anti-tumor therapy.

ACTA PHARMACEUTICA SINICA B (2021)

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Article Pathology

Diagnosis and therapy of tumors with NTRK gene fusion

Albrecht Stenzinger et al.

Summary: NTRK gene fusions are rare in most solid tumors but more common in certain rare tumors, acting as strong oncogenic drivers. TRK inhibitors like entrectinib and larotrectinib have shown effectiveness, with larotrectinib being approved in the EU. The low prevalence of TRK fusion-positive cancers presents challenges for diagnostic and clinical workflows.

PATHOLOGE (2021)

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Letter Oncology

Building on recent cytomorphologic descriptions of NTRK-rearranged thyroid carcinoma

Darcy A. Kerr et al.

CANCER CYTOPATHOLOGY (2021)

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Review Oncology

Tropomyosin Receptor Kinase Inhibitors for the Treatment of TRK Fusion Cancer

Theodore W. Laetsch et al.

Summary: Chromosomal rearrangements of NTRK1-3 resulting in gene fusions have been validated as oncogenic drivers in human cancers. Two TRK inhibitors have been approved for treating patients with solid tumors harboring NTRK gene fusions, highlighting the importance of detecting these fusions and understanding the pharmacological properties of TRK inhibitors.

CLINICAL CANCER RESEARCH (2021)

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Article Endocrinology & Metabolism

NTRK fusion analysis reveals enrichment in Middle Eastern BRAF wild-type PTC

Yan Kong et al.

Summary: This study reveals the presence of NTRK fusions in Middle Eastern PTC, particularly enriched in BRAF WT and pediatric age group, and suggests the utility of immunohistochemistry for screening PTC patients with NTRK fusion who may benefit from TRK inhibitors.

EUROPEAN JOURNAL OF ENDOCRINOLOGY (2021)

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Review Pathology

NTRK fusions and Trk proteins: what are they and how to test for them

Lawrence M. Weiss et al.

Summary: NTRK genes play a crucial role in various solid tumors, with fusions involving partner genes leading to upregulation of three proteins. Testing for NTRK fusions has become important due to FDA-approved treatments available, with RNA-based next-generation sequencing considered the gold standard for identification.

HUMAN PATHOLOGY (2021)

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Article Multidisciplinary Sciences

FusionAI: Predicting fusion breakpoint from DNA sequence with deep learning

Pora Kim et al.

Summary: The study introduces FusionAI, a deep learning model for predicting gene fusion breakpoints based on DNA sequences, with the goal of facilitating research on genomic breakages.

ISCIENCE (2021)

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Review Oncology

Liquid Biopsy: From Discovery to Clinical Application

Catherine Alix-Panabieres et al.

Summary: CTC and ctDNA have been recognized as promising biomarkers with various clinical applications, including early cancer detection and therapeutic monitoring. However, challenges such as standardization and validation of clinical effectiveness need to be addressed in this dynamic field of translational cancer research.

CANCER DISCOVERY (2021)

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Article Anatomy & Morphology

Fluorescent In Situ Hybridization Must be Preferred to pan-TRK Immunohistochemistry to Diagnose NTRK3-rearranged Gastrointestinal Stromal Tumors (GIST)

Marine Castillon et al.

Summary: Tyrosine kinase inhibitors have transformed the treatment of gastrointestinal stromal tumors (GISTs), and targeting TRK chimeric proteins from NTRK gene fusions offers a promising approach for patients without typical driver mutations. Testing for NTRK rearrangements using fluorescent in situ hybridization appears to be a valuable strategy for identifying treatable cases of GISTs lacking common mutations in KIT, PDGFRA, or BRAF.

APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY (2021)

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Article Endocrinology & Metabolism

Detection of Circulating Tumor DNA in Patients with Thyroid Nodules

Krupal B. Patel et al.

Summary: Detection of BRAF (V600E) circulating thyroid tumor DNA in plasma is correlated with the final diagnosis of classical variant of PTC, suggesting its utility as a tumor marker.

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (2021)

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Article Health Care Sciences & Services

Limited Clinical and Diagnostic Utility of Circulating Tumor DNA Detection in Patients with Early-Stage Well-Differentiated Thyroid Cancer: Comparison with Benign Thyroid Nodules and Healthy Individuals

Yong Joon Suh et al.

Summary: Limited data are available on the diagnostic utility of circulating tumor DNA (ctDNA) in early-stage thyroid cancers for specific mutations. The study found that circulating markers did not accurately reflect the mutational profile of primary or metastatic thyroid cancers, suggesting limited clinical utility for the analysis of specific mutations on ctDNA in early-stage thyroid cancers.

HEALTHCARE (2021)

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Article Oncology

TRK Fusions Are Enriched in Cancers with Uncommon Histologies and the Absence of Canonical Driver Mutations

Ezra Y. Rosen et al.

CLINICAL CANCER RESEARCH (2020)

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Editorial Material Oncology

NTRK gene fusions: a rough diamond ready to sparkle

Christian Rolfo

LANCET ONCOLOGY (2020)

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Article Oncology

Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials

David S. Hong et al.

LANCET ONCOLOGY (2020)

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Article Oncology

Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials

Robert C. Doebele et al.

LANCET ONCOLOGY (2020)

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Article Endocrinology & Metabolism

AIBx, Artificial Intelligence Model to Risk Stratify Thyroid Nodules

Johnson Thomas et al.

THYROID (2020)

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Review Endocrinology & Metabolism

Update on Fundamental Mechanisms of Thyroid Cancer

Alessandro Prete et al.

FRONTIERS IN ENDOCRINOLOGY (2020)

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Article Oncology

US Phase I First-in-human Study of Taletrectinib (DS-6051b/AB-106), a ROS1/TRK Inhibitor, in Patients with Advanced Solid Tumors

Kyriakos P. Papadopoulos et al.

CLINICAL CANCER RESEARCH (2020)

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Article Oncology

Fine needle aspiration cytomorphology of papillary thyroid carcinoma withNTRKgene rearrangement from a case series with predominantly indeterminate cytology

Rita Abi-Raad et al.

CANCER CYTOPATHOLOGY (2020)

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Article Oncology

Cytomorphologic features ofNTRK-rearranged thyroid carcinoma

Kartik Viswanathan et al.

CANCER CYTOPATHOLOGY (2020)

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Article Endocrinology & Metabolism

RET,NTRK,ALK,BRAF, andMETFusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas

Barbora Pekova et al.

THYROID (2020)

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Letter Medicine, General & Internal

Larotrectinib-Enhanced Radioactive Iodine Uptake in Advanced Thyroid Cancer

Lionel Groussin et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Multidisciplinary Sciences

Lymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics

Jinhua Yu et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

Artificial intelligence to predict the BRAFV600E mutation in patients with thyroid cancer

Jiyoung Yoon et al.

PLOS ONE (2020)

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Review Oncology

A systematic review and meta-analysis of neurotrophic tyrosine receptor kinase gene fusion frequencies in solid tumors

Anna Forsythe et al.

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY (2020)

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Article Chemistry, Medicinal

Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development and Clinical Application

Wei Yan et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

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Article Oncology

ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research

C. Marchio et al.

ANNALS OF ONCOLOGY (2019)

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Review Oncology

Detection of NTRK Fusions: Merits and Limitations of Current Diagnostic Platforms

James P. Solomon et al.

CANCER RESEARCH (2019)

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Article Pharmacology & Pharmacy

Entrectinib: First Global Approval

Zaina T. Al-Salama et al.

DRUGS (2019)

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Article Biochemistry & Molecular Biology

Resistance to TRK inhibition mediated by convergent MAPK pathway activation

Emiliano Cocco et al.

NATURE MEDICINE (2019)

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Article Oncology

Artificial intelligence in digital pathology - new tools for diagnosis and precision oncology

Kaustav Bera et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2019)

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Review Oncology

Identifying patients with NTRK fusion cancer

J. P. Solomon et al.

ANNALS OF ONCOLOGY (2019)

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Review Oncology

Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer

A. Amatu et al.

ANNALS OF ONCOLOGY (2019)

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Article Oncology

Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

S. Filetti et al.

ANNALS OF ONCOLOGY (2019)

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Review Pathology

NTRK-Fusions - A new kid on the block

Bruno Maerkl et al.

PATHOLOGY RESEARCH AND PRACTICE (2019)

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Article Pharmacology & Pharmacy

Larotrectinib: First Global Approval

Lesley J. Scott

DRUGS (2019)

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Article Pathology

Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors

Erin R. Rudzinski et al.

AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2018)

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Article Oncology

Trends in thyroid cancer: Retrospective analysis of incidence and survival in Denmark 1980-2014

Christian Mirian et al.

CANCER EPIDEMIOLOGY (2018)

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Article Otorhinolaryngology

Analysis of circulating tumor DNA does not improve the clinical management of patients with locally advanced and metastatic papillary thyroid carcinoma

Vincenzo Condello et al.

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK (2018)

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Article Oncology

Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study

Theodore W. Laetsch et al.

LANCET ONCOLOGY (2018)

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Article Medicine, General & Internal

Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children

A. Drilon et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

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Article Oncology

Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibit ROS1/TRK/ALK Solvent-Front Mutations

Alexander Drilon et al.

CANCER DISCOVERY (2018)

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Review Oncology

NTRK fusion-positive cancers and TRK inhibitor therapy

Emiliano Cocco et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2018)

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Article Oncology

A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors

Alexander Drilon et al.

CANCER DISCOVERY (2017)

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Article Pathology

Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions

Jaclyn F. Hechtman et al.

AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2017)

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Article Oncology

Targeted Therapy in Thyroid Cancer: State of the Art

L. Valerio et al.

CLINICAL ONCOLOGY (2017)

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Article Pathology

Clinical and Morphologic Features of ETV6-NTRK3 Translocated Papillary Thyroid Carcinoma in an Adult Population Without Radiation Exposure

Raja R. Seethala et al.

AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2017)

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Article Oncology

Acquired Resistance to the TRK Inhibitor Entrectinib in Colorectal Cancer

Mariangela Russo et al.

CANCER DISCOVERY (2016)

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Article Oncology

What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC)

A. Drilon et al.

ANNALS OF ONCOLOGY (2016)

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Article Oncology

NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States

Manju L. Prasad et al.

CANCER (2016)

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Article Pathology

A Multiplexed Amplicon Approach for Detecting Gene Fusions by Next-Generation Sequencing

Carol Beadling et al.

JOURNAL OF MOLECULAR DIAGNOSTICS (2016)

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Article Pathology

Molecular Characterization of Sporadic Pediatric Thyroid Carcinoma with the DNA/RNA ThyroSeq v2 Next-Generation Sequencing Assay

Jennifer L. Picarsic et al.

PEDIATRIC AND DEVELOPMENTAL PATHOLOGY (2016)

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Review Oncology

NTRK gene fusions as novel targets of cancer therapy across multiple tumour types

Alessio Amatu et al.

ESMO OPEN (2016)

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Article Endocrinology & Metabolism

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

Gary L. Francis et al.

THYROID (2015)

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Article Oncology

ETV6-NTRK3 Is a Common Chromosomal Rearrangement in Radiation-Associated Thyroid Cancer

Rebecca J. Leeman-Neill et al.

CANCER (2014)

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Article Biochemistry & Molecular Biology

Integrated Genomic Characterization of Papillary Thyroid Carcinoma

Nishant Agrawal et al.

CELL (2014)

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Article Medicine, Research & Experimental

Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers

Julio C. Ricarte-Filho et al.

JOURNAL OF CLINICAL INVESTIGATION (2013)

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Article Pathology

Mammary Analog Secretory Carcinoma of Salivary Gland Origin With the ETV6 Gene Rearrangement by FISH: Expanded Morphologic and Immunohistochemical Spectrum of a Recently Described Entity

Ashton Connor et al.

AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2012)

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Article Oncology

Cytomorphological and molecular genetic findings in pediatric thyroid fine-needle aspiration

Sara E. Monaco et al.

CANCER CYTOPATHOLOGY (2012)

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Article Oncology

A fluorescence in situ hybridization study of ETV6-NTRK3 fusion gene in secretory breast carcinoma

N Makretsov et al.

GENES CHROMOSOMES & CANCER (2004)

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Article Oncology

Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma

C Tognon et al.

CANCER CELL (2002)

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Article Pathology

Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors

JM Bourgeois et al.

AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2000)

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