Review
Oncology
Yanhui Ma, Qi Zhang, Kexin Zhang, Yunzi Liang, Fangbing Ren, Jingwen Zhang, Chengxia Kan, Fang Han, Xiaodong Sun
Summary: Thyroid cancer is commonly associated with NTRK fusions, which are oncogenic drivers in various solid tumors. Current detection methods rely on RNA-based next-generation sequencing, and targeted therapy with tropomyosin receptor kinase inhibitors has shown promise. Overcoming drug resistance is a current research focus. However, there is a lack of standardized procedures for diagnosing and treating NTRK fusions in thyroid cancer. This review provides an overview of the current research progress, clinicopathological features, and detection and therapeutic options for NTRK fusion-positive thyroid cancer.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2023)
Article
Oncology
Victoria Casado-Medrano, Alison O'Neill, Stephen Halada, Theodore W. Laetsch, Andrew J. Bauer, Aime T. Franco
Summary: Pediatric and adult papillary thyroid cancer (PTC) differ in oncogenic drivers and genetic alterations, requiring further research and improvement in treatment models.
Article
Oncology
Marco Maria Germani, Chiara Boccaccio, Antonio Matrone, Eleonora Molinaro, Greta Ali, Mirella Giordano, Rossella Elisei, Gabriella Fontanini, Chiara Cremolini
Summary: This article presents a case of advanced papillary thyroid carcinoma initially misdiagnosed as metastatic lung adenocarcinoma with papillary features. Comprehensive genomic profiling revealed NTRK1-TMP3 fusion and comutation of the TERT promoter. The patient achieved meaningful and durable clinical benefit with tailored treatment targeting NTRK fusion.
Article
Oncology
Viktoria Florentine Koehler, Josefine Achterfeld, Natalie Sandner, Christine Koch, Jonas Paul Wiegmann, Philipp Ivanyi, Lukas Kaesmann, Renate Pusch, Dominik Wolf, Mihaela Chirica, Thomas Knoesel, Melanie-Christin Demes, Joerg Kumbrink, Thomas J. Vogl, Gesine Meyer, Christine Spitzweg, Joerg Bojunga, Matthias Kroiss
Summary: This study aims to describe the prevalence of NTRK gene fusions and the efficacy and safety of TRK inhibitor treatment in non-medullary, advanced thyroid cancer (TC) patients. The results showed that 8 out of 184 patients (4%) had NTRK gene fusions. Among the 6 patients treated with TRK inhibitors, 83% achieved objective response and the median PFS was 23 months. The conclusion of the study is that larotrectinib is an effective treatment option with a favorable safety profile for NTRK gene fusion-positive advanced TC patients after prior systemic treatment.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Nathan D. Seligson, Todd C. Knepper, Susanne Ragg, Christine M. Walko
Summary: Targeted therapies have revolutionized cancer treatment, with recent biomarker-driven, tissue-agnostic clinical trials marking a significant shift towards precision medicine. However, only a few tissue-agnostic indications have been approved by the FDA so far, highlighting challenges such as complex cancer biology, clinical trial design, and resistance mechanisms that future therapies targeting tissue-agnostic indications will need to overcome.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Endocrinology & Metabolism
Stephen Halada, Shoshana Leftin Dobkin, Julia A. Baran, Lindsay Sisko, Stephanie L. Robbins, Jordan B. Rapp, Lisa R. Young, Andrew J. Bauer
Summary: This case report describes a pediatric patient with ERC1::RET-positive classic papillary thyroid carcinoma who developed progressive respiratory symptoms and chest imaging abnormalities following radioactive iodine therapy. Despite empirical antibiotic and anti-inflammatory therapies, the patient remains symptomatic and shows evidence of pulmonary fibrosis on chest imaging.
HORMONE RESEARCH IN PAEDIATRICS
(2023)
Article
Oncology
Hanna Cho, Namkyoung Kim, Takashi Murakami, Taebo Sim
Summary: AZD4547, a selective inhibitor of FGFR, exhibits anti-tumor activity against cancers harboring NTRK fusion gene by directly inhibiting TRKs, leading to inhibition of cell proliferation, induction of apoptosis, and delay in tumor growth.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Hind M. Osman, Meral Tuncbilek
Summary: This study summarizes recent research on the newly approved selective tyrosine kinase inhibitor entrectinib, including its synthesis, mechanism of action, and clinical trials. Based on three clinical studies, entrectinib was found to have good tolerance and manageable safety profile, and it induced clinically meaningful responses in recurrent or advanced solid tumors associated with NTRK fusion-positive or ROS1+ NSCLC. It also demonstrated substantial efficacy in patients with CNS metastases.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Sophie O'Haire, Fanny Franchini, Yoon-Jung Kang, Julia Steinberg, Karen Canfell, Jayesh Desai, Stephen Fox, Maarten IJzerman
Summary: NTRK gene fusions are rare somatic mutations found in various cancer types, and targeted therapies for them are emerging. However, integrating these treatments into healthcare systems poses challenges due to uncertain prevalence and optimal testing methods. To address this, a systematic review was conducted to determine the prevalence of NTRK fusions and guide efficient diagnostic screening. The review included 160 studies and found that NTRK fusion-positive cancers are rare and widely distributed across solid tumors. However, small-scale and heterogeneous data make it difficult to predict prevalence accurately. Further large-scale, standardized genomic data are needed to better understand NTRK fusion epidemiology.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Kiat Hon Tony Lim, Hwai Loong Kong, Kenneth Tou En Chang, Daniel Shao Weng Tan, Iain Bee Huat Tan, Farid Mohamad, Shui Yen Soh, Brendan Nghee-Kheem Pang, Ross Andrew Soo, Su Pin Choo, Wen-Son Hsieh, LeLe Aung
Summary: NTRK gene fusions are detected in a wide range of tumor types, presenting an attractive option for using TRK inhibitors as cancer therapy. Clinical studies have shown efficacious outcomes with TRK inhibitors in NTRK fusion-bearing cancers. Testing for NTRK gene fusions in advanced malignancies is important but presents practical and financial challenges.
ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Zuqin Wang, Jie Wang, Yongjin Wang, Shuang Xiang, Hengliang Zhou, Shukai Song, Xiaojuan Song, Zhengchao Tu, Yang Zhou, Ke Ding, Zhi-Min Zhang, Zhang Zhang, Xiaoyun Lu
Summary: This study focuses on the development of new type II TRK inhibitors to combat acquired resistance mutations. Compound 10g displayed excellent potency against TRK mutants and demonstrated strong inhibition of cell proliferation. The results provide a promising lead compound for pan-anticancer drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Sun-Young Han
Summary: Recently approved Trk inhibitors, larotrectinib and entrectinib, have shown promising results for Trk fusion-positive cancer patients, using a tissue-agnostic development approach to expedite the drug development process. The on-target effects of Trk inhibitors on the central nervous system pose challenges, but a next generation sequencing-based companion diagnostic has been approved for detecting various types of Trk fusions. Through the adoption of tissue-agnostic approach, the development of Trk inhibitors has been accelerated.
Article
Oncology
Hedvig Elfving, Erika Brostrom, Lotte N. J. Moens, Jonas Almlof, Dijana Cerjan, Gilbert Lauter, Helena Nord, Johanna S. M. Mattsson, Gustav J. Ullenhag, Carina Strell, Max Backman, Linnea La Fleur, Hans Brunnstrom, Johan Botling, Patrick Micke
Summary: The presence of NTRK fusion genes in non-small cell lung cancer is exceedingly rare. The use of the immunohistochemical NTRK assay may result in a small number of false positive cases.
Article
Oncology
Guilherme Harada, Fernando C. Santini, Clare Wilhelm, Alexander Drilon
Summary: Fusions involving TRK protein tyrosine kinases are oncogenic drivers in various tumors, with first-generation TRK inhibitors showing clinically meaningful antitumor activity but on-target resistance needs to be monitored. These inhibitors should be considered as first-line therapeutic options for TRK fusion-positive lung cancers, and next-generation TRK inhibitors are being studied for addressing resistance mechanisms.
Review
Pathology
Minh Anh Nguyen, Andrew J. Colebatch, Diana Van Beek, Geraldine Tierney, Ruta Gupta, Wendy A. Cooper
Summary: Fusions involving the NTRK gene family are targetable oncogenic alterations found in a diverse range of tumors. Identifying these fusions is challenging due to various genetic mechanisms, frequency differences, and other factors. Pathologists play a key role in determining optimal testing approaches with therapeutic and prognostic implications. This review provides an overview of tumors harboring NTRK fusions and available testing methods.
Article
Multidisciplinary Sciences
Ola Awad, Jason T. Yustein, Preeti Shah, Naheed Gul, Varalakshmi Katuri, Alison O'Neill, Yali Kong, Milton L. Brown, Jeffrey A. Toretsky, David M. Loeb
Article
Oncology
Jason U. Tilan, Congyi Lu, Susana Galli, Ewa Izycka-Swieszewska, Joshua Patrick Earnest, Asim Shabbir, Lindsay M. Everhart, Shuo Wang, Samantha Martin, Meredith Horton, Akanksha Mahajan, David Christian, Alison O'Neill, Hongkun Wang, Tingting Zhuang, Magdalena Czarnecka, Michael D. Johnson, Jeffrey A. Toretsky, Joanna Kitlinska
Article
Oncology
Victoria Casado-Medrano, Alison O'Neill, Stephen Halada, Theodore W. Laetsch, Andrew J. Bauer, Aime T. Franco
Summary: Pediatric and adult papillary thyroid cancer (PTC) differ in oncogenic drivers and genetic alterations, requiring further research and improvement in treatment models.
