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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Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization
Siraj M. Ali,Thomas A. Hensing,Thomas A. Hensing,Alexa B. Schrock,Justin M. Allen,Eric M. Sanford,Kyle Gowen,Atul Kulkarni,Jie He,James Suh,Doron Lipson,Julia A. Elvin,Roman Yelensky,Zachary R. Chalmers,Juliann Chmielecki,Nir Peled,Samuel J. Klempner,Kashif Firozvi,Garrett M. Frampton,Julian R. Molina,Smitha Menon,Julie R. Brahmer,Heber MacMahon,Jan A. Nowak,Sai-Hong Ignatius Ou,Marjorie G. Zauderer,Marc Ladanyi,Maureen F. Zakowski,Neil Fischbach,Jeffrey S. Ross,Jeffrey S. Ross,Phil Stephens,Vincent A. Miller,Heather A. Wakelee,Shridar Ganesan,Ravi Salgia +35 more
TL;DR: Combined genomic profiling that includes hybrid capture and specific baiting of intron 19 of ALK is a highly sensitive, alternative method for identification of drug-sensitive ALK fusions in patients with non-small cell lung cancer who had previously tested negative using standard ALK fluorescence in situ hybridization (FISH) diagnostic assays.
Journal ArticleDOI
Oncogenic ALK Fusion in Rare and Aggressive Subtype of Colorectal Adenocarcinoma as a Potential Therapeutic Target
Evgeny Yakirevich,Murray B. Resnick,Shamlal Mangray,Michael Wheeler,Cynthia L. Jackson,Kara Lombardo,Jeeyun Lee,Kyoung-Mee Kim,Anthony J. Gill,Kai Wang,Kyle Gowen,James Sun,Vincent A. Miller,Philip J. Stephens,Siraj M. Ali,Jeffrey S. Ross,Howard Safran +16 more
TL;DR: This report provides the first clinical evidence that patients with refractory metastatic colorectal carcinoma harboring a STRN–ALK gene fusion who achieved an exceptional clinical benefit to the ALK inhibitor ceritinib may benefit from targeted monotherapy with ALK inhibitors.
Journal ArticleDOI
Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors
Monika A. Davare,Nadeem A. Vellore,Jacob P. Wagner,Christopher A. Eide,Christopher A. Eide,James R. Goodman,Alexander Drilon,Michael W. Deininger,Thomas O'Hare,Brian J. Druker,Brian J. Druker +10 more
TL;DR: In this article, the sensitivity and selectivity of seven ROS1 and/or ALK inhibitors at various levels of clinical development were analyzed. And the authors showed that the ROS1-selective inhibitors retain efficacy against the recently reported CD74-ROS1(G2032R) mutant whereas the dual ROS1/ALK inhibitors are ineffective.
Journal ArticleDOI
Infantile Fibrosarcoma With NTRK3-ETV6 Fusion Successfully Treated With the Tropomyosin-Related Kinase Inhibitor LOXO-101.
Ramamoorthy Nagasubramanian,Julie Wei,Paul Gordon,Jeffrey C. Rastatter,Michael C. Cox,Alberto S. Pappo +5 more
TL;DR: A case of refractory IFS with constitutive activation of the tropomyosin‐related kinase (TRK) signaling pathway from an ETS variant gene 6–neurotrophin 3 receptor gene (ETV6–NTRK3) gene fusion is reported.
Journal ArticleDOI
Gene fusions in soft tissue tumors: Recurrent and overlapping pathogenetic themes
TL;DR: The present review provides an overview of the spectrum of currently recognized gene fusions in STT, and, on the basis of the protein class involved, the mechanisms by which they exert their oncogenic effect are discussed.
References
More filters
Journal ArticleDOI
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.
TL;DR: The results for 20 world regions are presented, summarizing the global patterns for the eight most common cancers, and striking differences in the patterns of cancer from region to region are observed.
Journal ArticleDOI
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Manabu Soda,Young Lim Choi,Munehiro Enomoto,Shuji Takada,Yoshihiro Yamashita,Shunpei Ishikawa,Shin-ichiro Fujiwara,Hideki Watanabe,Kentaro Kurashina,Hisashi Hatanaka,Masashi Bando,Shoji Ohno,Yuichi Ishikawa,Hiroyuki Aburatani,Toshiro Niki,Yasunori Sohara,Yukihiko Sugiyama,Hiroyuki Mano +17 more
TL;DR: It is shown that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells.
Journal ArticleDOI
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Eunice L. Kwak,Yung-Jue Bang,D. Ross Camidge,Alice T. Shaw,Benjamin Solomon,Robert G. Maki,Sai-Hong Ignatius Ou,Bruce J. Dezube,Pasi A. Jänne,Daniel B. Costa,Marileila Varella-Garcia,Woo-Ho Kim,Thomas J. Lynch,Panos Fidias,Hannah Stubbs,Jeffrey A. Engelman,Lecia V. Sequist,Weiwei Tan,Leena Gandhi,Mari Mino-Kenudson,Greg C. Wei,S. Martin Shreeve,Mark J. Ratain,Jeffrey Settleman,James G. Christensen,Daniel A. Haber,Keith D. Wilner,Ravi Salgia,Geoffrey I. Shapiro,Jeffrey W. Clark,A. John Iafrate +30 more
TL;DR: The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients, and the drug resulted in grade 1 or 2 gastrointestinal side effects.
Journal ArticleDOI
Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer
Alice T. Shaw,Dong Wan Kim,Kazuhiko Nakagawa,Takashi Seto,Lucio Crinò,Myung-Ju Ahn,Tommaso De Pas,Benjamin Besse,Benjamin Solomon,Fiona H Blackhall,Yi-Long Wu,Michael Thomas,Kenneth J. O'Byrne,Denis Moro-Sibilot,D. Ross Camidge,Tony Mok,Vera Hirsh,Gregory J. Riely,Shrividya Iyer,V. Tassell,Anna Polli,Keith D. Wilner,Pasi A. Jänne +22 more
TL;DR: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement and greater improvement in global quality of life with crizotinIB than with chemotherapy.
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