Tyrosine kinase gene rearrangements in epithelial malignancies
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TLDR
The clinical outcomes with targeted therapies, aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET are examined.Abstract:
In this Review, the authors examine the aetiological, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, the clinical outcomes with targeted therapies, and strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours. Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as 'druggable' targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours.read more
Citations
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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
TL;DR: Entrectinib was shown to be well tolerated and active against those gene fusions in solid tumors, including in patients with primary or secondary CNS disease, and a complete CNS response was achieved in a patient with SQSTM1-NTRK1-rearranged lung cancer.
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TL;DR: The spectrum of gene fusions in cancer and how the methods to identify them have evolved are described, and the conceptual implications of current, sequencing-based approaches for detection are discussed.
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The landscape and therapeutic relevance of cancer-associated transcript fusions.
Kosuke Yoshihara,Qianghu Wang,Wandaliz Torres-Garcia,Siyuan Zheng,Rahulsimham Vegesna,Hoon Kim,Roel G.W. Verhaak +6 more
TL;DR: The landscape of transcript fusions detected across a large number of tumor samples was described and revealed fusion events with clinical relevance that have not been previously recognized, support the concept of basket clinical trials and reveal an important role for tumorigenesis.
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Spatial Organization of the Mouse Genome and Its Role in Recurrent Chromosomal Translocations
Yu Zhang,Rachel Patton McCord,Yu-Jui Ho,Bryan R. Lajoie,Dominic G. Hildebrand,Alince C. Simon,Michael B. Becker,Frederick W. Alt,Job Dekker +8 more
TL;DR: A high-resolution Hi-C spatial organization map of the G1-arrested mouse pro-B cell genome is generated and high-throughput genome-wide translocation sequencing is used to map translocations from target DNA double-strand breaks (DSBs) within it.
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Phase II Trial of Sorafenib in Metastatic Thyroid Cancer
Richard T. Kloos,Matthew D. Ringel,Michael V. Knopp,Nathan Hall,Mark A. King,Robert Stevens,Jiachao Liang,Paul E. Wakely,Vasyl Vasko,Motoyasu Saji,Jennifer Rittenberry,Lai Wei,Daria Arbogast,Minden Collamore,John J. Wright,Michael R. Grever,Manisha H. Shah +16 more
TL;DR: Sorafenib is reasonably well-tolerated therapy with clinical and biologic antitumor activity in metastatic PTC and four of 10 paired tumor biopsies from PTC patients showed a reduction in levels of vascular endothelial growth factor receptor phosphorylated, ERK phosphorylation, and in VEGF expression during sorafenIB therapy.
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