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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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
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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The emerging complexity of gene fusions in cancer
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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Erratum: Non-small-cell lung cancers: a heterogeneous set of diseases
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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.
References
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Journal ArticleDOI
Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes.
Isaac A. Klein,Wolfgang Resch,Mila Jankovic,Thiago Y. Oliveira,Thiago Y. Oliveira,Arito Yamane,Hirotaka Nakahashi,Michela Di Virgilio,Anne Bothmer,André Nussenzweig,Davide F. Robbiani,Rafael Casellas,Michel C. Nussenzweig,Michel C. Nussenzweig +13 more
TL;DR: Translocation Capture Sequencing (TC-Seq) as mentioned in this paper is a method to document chromosomal rearrangements genome-wide, in primary cells in B cell lymphoma, revealing that proximity between DSBs, transcriptional activity and chromosome territories are key determinants of genome rearrangement.
The Extent and Nature Of Chromosomal Rearrangements in B Lymphocytes
TL;DR: Translocation Capture Sequencing (TC-Seq) is developed, a method to document chromosomal rearrangements genome-wide, in primary cells and finds that activation-induced cytidine deaminase (AID) induces the rearrangement of many genes found as translocation partners in mature B cell lymphoma.
Journal Article
High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident
TL;DR: Intrachromosomal rearrangement involving RET and the adjacent H4 or ELE gene on chromosome no. 10 is a very frequent event in thyroid cancer of children of the Chernobyl-contaminated zone of Belarus.
Journal ArticleDOI
Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers.
Eva Lin,Li Li,Yinghui Guan,Robert Soriano,Celina Sanchez Rivers,Sankar Mohan,Ajay Pandita,Jerry Tang,Zora Modrusan +8 more
TL;DR: Findings show the recurrence of EML4-ALK fusion in multiple solid tumors and further substantiate its role in tumorigenesis, as well as elucidate the functional significance of the gene.
Journal ArticleDOI
Ponatinib (AP24534), a Multitargeted Pan-FGFR Inhibitor with Activity in Multiple FGFR-Amplified or Mutated Cancer Models
Joseph M. Gozgit,Matthew J. Wong,Lauren Moran,Scott Wardwell,Qurish K. Mohemmad,Narayana I. Narasimhan,William C. Shakespeare,Frank Wang,Tim Clackson,Victor M. Rivera +9 more
TL;DR: Results show that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers.
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