J Med Chem 2019 Sep 19;62(17):8364. Epub 2019 Aug 19.
Eur J Med Chem 2021 Apr 9;216:113265. Epub 2021 Feb 9.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address:
Tropomyosin receptor kinase (TRK) represents an attractive oncology target for cancer therapy related to its critical role in cancer formation and progression. NTRK fusions are found to occur in 3.3% of lung cancers, 2. Read More
Hum Pathol 2021 Mar 7;109:37-44. Epub 2020 Dec 7.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582 Japan.
Salivary secretory carcinoma (SASC) is frequently associated with ETV6-neurotrophic tyrosine receptor kinase (NTRK) 3 fusion and more rarely with RET, MET, or ALK rearrangement. We aimed to elucidate the potential diagnostic utility of pan-tropomyosin receptor kinase (Trk) immunohistochemistry and its relationship with the fusion gene subtype in SASC. We examined 33 cases of SASC for immunoexpression of pan-Trk, ALK and ROS1, and gene rearrangement of the ETV6, NTRK3, and RET genes using fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). Read More
Sci Rep 2020 10 30;10(1):18724. Epub 2020 Oct 30.
Department of Human Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
Gene expression imbalances were measured for tyrosine kinase (TK) genes using Nanostring in 19 samples of inflammatory myofibroblastic tumor (IMT). All cases were immunohistochemically stained with anaplastic lymphoma kinase (ALK) and pan-tropomyosin-related-kinase (pan-Trk) antibodies. Five cases with imbalanced ALK expression, reported with Nanostring, were tested using fluorescence in situ hybridization (FISH); two cases with imbalanced neurotrophic tyrosine receptor kinase 3 (NTRK3) expression were tested using reverse transcription-polymerase chain reaction (RT-PCR). Read More
Clin Drug Investig 2020 Jun;40(6):519-527
Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK.
In the evolving landscape of precision oncology, genomic characterization of tumor has become crucial in order to move toward a molecular-based therapy for the vast majority of cancers. Recently, translational research has offered new perspectives in systemic cancer treatment thanks to the identification of novel oncogenic targets and the development of new targeted therapies, followed by the latest applications of genomic sequencing. Simultaneously, next-generation sequencing (NGS) has expanded its accessibility, being incorporated into clinical studies at the time of the initial screening, disease progression, and often in longitudinal monitoring of molecular changes. Read More
J Pharmacol Exp Ther 2020 06 26;373(3):361-369. Epub 2020 Mar 26.
Clinical Pharmacology (H.I., T.O.), Research Center of Oncology (R.F., R.K.), and Pharmacokinetic Research Laboratories (R.H., Y.H.), Ono Pharmaceutical Company Limited, Osaka, Japan; and Laboratory of Pharmaceutics, Kobe Pharmaceutical University, Higashinada-ku, Kobe, Japan (H.I., K.O.).
The orally available and novel small molecule ONO-7579 (-{2-[4-(2-amino-5-chloropyridin-3-yl)phenoxy]pyrimidin-5-yl}-'-[2-(methanesulfonyl)-5-(trifluoromethyl)phenyl]urea) is a highly potent and selective pan-tropomyosin receptor kinase (TRK) inhibitor. The objective of the present study was to characterize the pharmacokinetic (PK), pharmacodynamic (PD), and antitumor efficacy relationships of ONO-7579 in mice xenografted with a human colorectal cancer cell line, KM12 (harboring the tropomyosin 3 neurotrophic tyrosine receptor kinase 1 fusion gene), via a PK/PD modeling approach. Plasma and tumor concentrations of ONO-7579, tumor levels of phosphorylated TPM3-TRKA (pTRKA), and tumor volumes in the murine model were measured with a single or multiple dose of ONO-7579 (0. Read More