Journal ArticleDOI
Targeting TRK family proteins in cancer.
Yekaterina B. Khotskaya,Vijaykumar Holla,Anna F. Farago,Kenna R. Mills Shaw,Funda Meric-Bernstam,David S. Hong +5 more
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TLDR
Selective inhibition of TRK signaling may be beneficial among patients whose tumors vary in histologies, but share underlying oncogenic NTRK gene alterations, as well as several TRK‐targeting compounds in clinical development.About:
This article is published in Pharmacology & Therapeutics.The article was published on 2017-05-01. It has received 193 citations till now. The article focuses on the topics: Trk receptor & Entrectinib.read more
Citations
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Journal ArticleDOI
Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials
Robert C. Doebele,Alexander Drilon,Alexander Drilon,Luis Paz-Ares,Salvatore Siena,Alice T. Shaw,Anna F. Farago,Collin M. Blakely,Takashi Seto,Byung Chul Cho,D. Tosi,Benjamin Besse,Sant P. Chawla,Lyudmila Bazhenova,John C. Krauss,Young Kwang Chae,Minal A. Barve,Ignacio Garrido-Laguna,Stephen V. Liu,Paul Conkling,Thomas John,Marwan Fakih,Darren Sigal,Herbert H. Loong,Gary L Buchschacher,Pilar Garrido,Jorge Nieva,Conor E. Steuer,Tobias Overbeck,Daniel W. Bowles,Elizabeth Fox,Todd Riehl,Edna Chow-Maneval,B. Simmons,Na Cui,Ann M. Johnson,Susan Eng,Timothy R. Wilson,George D. Demetri +38 more
TL;DR: Results show that entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile.
Journal ArticleDOI
ERK/MAPK signalling pathway and tumorigenesis.
TL;DR: The present review discusses recent studies on Ras and ERK pathway members and the role of the ERK/MAPK signalling pathway in tumour extracellular matrix degradation and tumour angiogenesis is emphasised.
Journal ArticleDOI
Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.
Lei Zhong,Y. Li,Liang Xiong,Wen-Jing Wang,Ming Wu,Ting Yuan,Wei Yang,Chenyu Tian,Zhuang Miao,Tianqi Wang,Shengyong Yang +10 more
TL;DR: A comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification is conducted, which presents all the approved drugs as well as important drug candidates in clinical trials for each target, and discusses the current challenges.
Journal ArticleDOI
Molecular characterization of cancers with NTRK gene fusions.
TL;DR: The rarity of NTRK genes fusions outside the brain malignancies is confirmed and strategies for detection of the N TRK fusion-driven cancers may include immunohistochemistry, but gene fusion detection remains the most reliable tool.
Journal ArticleDOI
Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions.
Jaclyn F. Hechtman,Ryma Benayed,David M. Hyman,Alexander Drilon,Ahmet Zehir,Denise Frosina,Maria E. Arcila,Snjezana Dogan,David S. Klimstra,Marc Ladanyi,Achim A. Jungbluth +10 more
TL;DR: Pan-Trk IHC is a time-efficient and tissue-efficient screen for NTRK fusions, particularly in driver-negative advanced malignancies and potential cases of secretory carcinoma and congenital fibrosarcoma, and can help determine whether translation occurs for novel N TRK rearrangements.
References
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Journal ArticleDOI
The treatment of suicidality in adolescents by psychosocial interventions for depression: a systematic literature review
TL;DR: There is evidence to suggest that Cognitive Behavioural Therapy interventions produce pre–post reductions in suicidality with moderate effect sizes and are at least as efficacious as pharmacotherapy in reducing suicideality; however, it is unclear whether these effects are sustained.
Proceedings ArticleDOI
Abstract PR13: Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions
David S. Hong,Marcia S. Brose,Robert C. Doebele,Alice T. Shaw,Afshin Dowlati,Todd M. Bauer,Anna F. Farago,Adriana Estrada-Bernal,Anh T. Lee,Michael C. Cox,Nisha Nanda,Jennifer A. Low,Howard A. Burris +12 more
TL;DR: LAXO-101 has been well tolerated and has sufficient systemic exposure for robust tumor responses in 3 of 3 (100%) of NTRK-fusion pts enrolled on study, and further validate this molecular target as an oncogenic driver across diverse tumor histologies.
Journal ArticleDOI
Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions
David S. Hong,A. Dowlati,Howard A. Burris,James J. Lee,Marcia S. Brose,Anna F. Farago,Todd M. Bauer,Michelle Taylor,Alice T. Shaw,S. Smith,N. Nanda,S. Cruikshank,Michael C. Cox,Robert C. Doebele +13 more
Journal ArticleDOI
In vitro and in vivo effects of bicalutamide on the expression of TrkA and P75 neurotrophin receptors in prostate carcinoma
Claudio Festuccia,Giovanni Luca Gravina,Paola Muzi,Roberto Pomante,Luca Ventura,Enrico Ricevuto,Carlo Vicentini,Mauro Bologna +7 more
TL;DR: Neurotrophine tyrosine kinase receptors (NTR) are expressed in prostate carcinoma (PCa), and their distribution seems to be related to disease malignancy.
Journal ArticleDOI
Mutations in NTRK3 suggest a novel signaling pathway in human congenital heart disease.
Petra Werner,Prasuna Paluru,Anisha M. Simpson,Brande Latney,Radhika Iyer,Garrett M. Brodeur,Elizabeth Goldmuntz +6 more
TL;DR: Functional analysis using neuroblastoma cell lines expressing mutant TrkC demonstrated that one of the mutations significantly reduced autophosphorylation in response to ligand binding, subsequently decreasing phosphorylation of downstream target proteins.
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Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children
Alexander Drilon,Theodore W. Laetsch,Shivaani Kummar,Steven G. DuBois,Ulrik Lassen,George D. Demetri,Michael J. Nathenson,Robert C. Doebele,Anna F. Farago,Alberto S. Pappo,Brian Turpin,Afshin Dowlati,Marcia S. Brose,Leo Mascarenhas,Noah Federman,Jordan Berlin,Wafik S. El-Deiry,Christina S. Baik,John F. Deeken,Valentina Boni,Ramamoorthy Nagasubramanian,Matthew H. Taylor,Erin R. Rudzinski,Funda Meric-Bernstam,Davendra Sohal,Patrick C. Ma,Luis E. Raez,Jaclyn F. Hechtman,Ryma Benayed,Marc Ladanyi,Brian B. Tuch,Kevin Ebata,Scott Cruickshank,Nora Ku,Michael C. Cox,Douglas S. Hawkins,David S. Hong,David S. Hong,David M. Hyman +38 more
TRKing Down an Old Oncogene in a New Era of Targeted Therapy
Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1).
Alexander Drilon,Salvatore Siena,Sai-Hong Ignatius Ou,Manish Patel,Myung-Ju Ahn,Jeeyun Lee,Todd M. Bauer,Anna F. Farago,Jennifer J. Wheler,Stephen V. Liu,Robert C. Doebele,Laura Giannetta,Giulio Cerea,Giovanna Marrapese,Michele Schirru,Alessio Amatu,Katia Bencardino,Laura Palmeri,Andrea Sartore-Bianchi,Angelo Vanzulli,Sara Cresta,Silvia Damian,Matteo Duca,Elena Ardini,Gang Li,Jason Christiansen,Karey Kowalski,Ann D. Johnson,Rupal Patel,David Luo,Edna Chow-Maneval,Zachary Hornby,Pratik S. Multani,Alice T. Shaw,Filippo de Braud +34 more
Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.
Aria Vaishnavi,Marzia Capelletti,Anh T. Le,Severine Kako,Mohit Butaney,Dalia Ercan,Sakshi Mahale,Kurtis D. Davies,Dara L. Aisner,Dara L. Aisner,Amanda B. Pilling,Eamon M. Berge,Jhingook Kim,Hidefumi Sasaki,Seung-Il Park,Gregory V. Kryukov,Levi A. Garraway,Levi A. Garraway,Peter S. Hammerman,Julia Haas,Steven W. Andrews,Doron Lipson,Philip J. Stephens,V.A. Miller,Marileila Varella-Garcia,Marileila Varella-Garcia,Pasi A. Jänne,Robert C. Doebele,Robert C. Doebele +28 more