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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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
KIF5B-ALK, a Novel Fusion Oncokinase Identified by an Immunohistochemistry-based Diagnostic System for ALK-positive Lung Cancer
Kengo Takeuchi,Young Lim Choi,Yuki Togashi,Manabu Soda,Satoko Hatano,Kentaro Inamura,Shuji Takada,Toshihide Ueno,Yoshihiro Yamashita,Yukitoshi Satoh,Sakae Okumura,Ken Nakagawa,Yuichi Ishikawa,Hiroyuki Mano +13 more
TL;DR: An intercalated antibody-enhanced polymer (iAEP) method that incorporates an intercalating antibody between the primary antibody to ALK and the dextran polymer-based detection reagents should prove suitable for immunohistochemical screening of tumors positive for ALK or ALK fusion proteins among pathologic archives.
Journal ArticleDOI
Transforming fusions of FGFR and TACC genes in human glioblastoma
Devendra Singh,Joseph M. Chan,Pietro Zoppoli,Francesco Niola,Francesco Niola,Ryan J. Sullivan,Angelica Castano,Eric Minwei Liu,Jonathan Reichel,Jonathan Reichel,Paola Porrati,Serena Pellegatta,Kunlong Qiu,Zhibo Gao,Michele Ceccarelli,Riccardo Riccardi,Daniel J. Brat,Abhijit Guha,Kenneth Aldape,John G. Golfinos,David Zagzag,Tom Mikkelsen,Gaetano Finocchiaro,Anna Lasorella,Raul Rabadan,Antonio Iavarone +25 more
TL;DR: In mice, FGFR inhibitors slowed the growth of tumors driven by the TACC-FGFR gene, suggesting that a subset of glioblastoma patients may benefit from these types of drugs, and a fusion gene detected in a small subset of human brain tumors encodes a potentially druggable target.
Journal ArticleDOI
Thyroid cancer after Chernobyl
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Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma
James G. Christensen,Helen Y. Zou,Maria E. Arango,Qiuhua Li,Joseph H. Lee,Scott Rp McDonnell,Shinji Yamazaki,Gordon Alton,Barbara Mroczkowski,Gerrit Los +9 more
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TL;DR: It is shown that activation of the ERK1/2 pathway is both necessary and sufficient to promote BimEL phosphorylation and that this leads to a substantial increase in turnover of the BIMEL protein.
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