Tyrosine kinase gene rearrangements in epithelial malignancies
Reads0
Chats0
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
More filters
Journal ArticleDOI
Non-small-cell lung cancers: a heterogeneous set of diseases
TL;DR: An impressive list of potential therapeutic targets was unveiled, drastically altering the clinical evaluation and treatment of patients for non-small-cell lung cancers, including immunotherapy.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
Erratum: Non-small-cell lung cancers: a heterogeneous set of diseases
TL;DR: ADCs can be modelled by KrasG12D expression (long latency), KrasD expression and Trp53-null, and epidermal growth factor receptor (EGFR)T790M/L858R, among other genetic models, and they are thought to arise from more distal airway cells.
Journal ArticleDOI
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
More filters
Journal ArticleDOI
The multifaceted roles of the receptor tyrosine kinase ROS in development and cancer.
TL;DR: The various roles that this receptor plays in multiple system networks in normalcy and disease are highlighted and points to future directions towards the elucidation of ROS function in the context of ligand identification, signaling pathways and clinical applications.
Journal ArticleDOI
Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC).
Dong Wan Kim,Myung-Ju Ahn,Yuankai Shi,Tommaso De Pas,Pan-Chyr Yang,Gregory J. Riely,Lucio Crinò,Tracey L. Evans,Xiaoqing Liu,Ji-Youn Han,Ravi Salgia,Denis Moro-Sibilot,Sai-Hong Ignatius Ou,Scott N. Gettinger,Yi-Long Wu,Silvana Lanzalone,Anna Polli,Shrividya Iyer,Alice T. Shaw +18 more
TL;DR: ProFILE 1005 is an ongoing global, multicenter, open-label, single-arm, phase II study evaluating the safety and efficacy of crizotinib (250 mg BID in 3-week cycles) in patients with advanced ALK-positive NSCLC who progressed after ≥1 chemotherapy for recurrent/advanced/metastatic disease.
Journal ArticleDOI
Inhibition of ALK, PI3K/MEK and HSP90 in Murine Lung Adenocarcinoma Induced by EML4-ALK Fusion Oncogene
Zhao Chen,Takaaki Sasaki,Xiaohong Tan,Julian Carretero,Takeshi Shimamura,Danan Li,Chunxiao Xu,Yuchuan Wang,Guillaume Adelmant,Marzia Capelletti,Hyun Joo Lee,Scott J. Rodig,Christa L. Borgman,Seung-Il Park,Hyeong Ryul Kim,Robert F. Padera,Jarrod A. Marto,Nathanael S. Gray,Andrew L. Kung,Geoffrey I. Shapiro,Pasi A. Jänne,Kwok-Kin Wong +21 more
TL;DR: A murine model is defined that offers a reliable platform for the preclinical comparison of combinatorial treatment approaches for lung cancer characterized by ALK rearrangement and treatment with geldanamycin-based HSP90 inhibitors.
Journal ArticleDOI
Genomic landscape of non-small-cell lung cancer in smokers and never-smokers
TL;DR: Smokers had an average mutation frequency 10-fold higher than never-smokers and a significantly higher chance of developing non-small-cell lung cancer.
Journal ArticleDOI
The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas.
TL;DR: This is the first report on two novel types of RET rearrangement, PTC6 and 7, and the fusion products and the ret fused gene (rfg) proteins, which are involved in human thyroid carcinogenesis.
Related Papers (5)
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
RET, ROS1 and ALK fusions in lung cancer.
Crizotinib in ROS1-Rearranged Non–Small-Cell Lung Cancer
Alice T. Shaw,Sai-Hong Ignatius Ou,Yung-Jue Bang,D. Ross Camidge,Benjamin Solomon,Ravi Salgia,Gregory J. Riely,Marileila Varella-Garcia,Geoffrey I. Shapiro,Daniel B. Costa,Robert C. Doebele,Long P. Le,Zongli Zheng,Zongli Zheng,Weiwei Tan,Patricia Stephenson,S. Martin Shreeve,L. Tye,James G. Christensen,Keith D. Wilner,Jeffrey W. Clark,A. John Iafrate +21 more
Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Klarisa Rikova,Ailan Guo,Qingfu Zeng,Anthony Possemato,Jian Yu,Herbert Haack,Julie Nardone,Kimberly Lee,Cynthia Reeves,Yu Li,Yerong Hu,Zhi-Ping Tan,Matthew P. Stokes,Laura Sullivan,Jeffrey Mitchell,Randy Wetzel,Joan MacNeill,Jian Min Ren,Jin Yuan,Corey E. Bakalarski,Judit Villén,Jon M. Kornhauser,Bradley L. Smith,Daiqiang Li,Xinmin Zhou,Steven P. Gygi,Ting-Lei Gu,Roberto D. Polakiewicz,John Rush,Michael J. Comb +29 more
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