The consensus molecular subtypes of colorectal cancer
Justin Guinney,Rodrigo Dienstmann,Rodrigo Dienstmann,Xingwu Wang,Xingwu Wang,Aurélien de Reyniès,Andreas Schlicker,Charlotte Soneson,Laetitia Marisa,Paul Roepman,Gift Nyamundanda,Paolo Angelino,Brian M. Bot,Jeffrey S. Morris,Iris Simon,Sarah Gerster,Evelyn Fessler,Felipe De Sousa E Melo,Edoardo Missiaglia,Hena R. Ramay,David Barras,Krisztian Homicsko,Dipen M. Maru,Ganiraju C. Manyam,Bradley M. Broom,Valérie Boige,Beatriz Perez-Villamil,Ted Laderas,Ramon Salazar,Joe W. Gray,Douglas Hanahan,Josep Tabernero,René Bernards,Stephen H. Friend,Pierre Laurent-Puig,Jan Paul Medema,Anguraj Sadanandam,Lodewyk F. A. Wessels,Mauro Delorenzi,Mauro Delorenzi,Scott Kopetz,Louis Vermeulen,Sabine Tejpar +42 more
TLDR
An international consortium dedicated to large-scale data sharing and analytics across expert groups is formed, showing marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features.Abstract:
Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions.read more
Citations
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Understanding the tumor immune microenvironment (TIME) for effective therapy.
Mikhail Binnewies,Edward W. Roberts,Kelly Kersten,Vincent Chan,Douglas F. Fearon,Miriam Merad,Lisa M. Coussens,Dmitry I. Gabrilovich,Suzanne Ostrand-Rosenberg,Suzanne Ostrand-Rosenberg,Catherine C. Hedrick,Robert H. Vonderheide,Mikael J. Pittet,Rakesh K. Jain,Weiping Zou,T. Kevin Howcroft,Elisa C. Woodhouse,Robert A. Weinberg,Matthew F. Krummel +18 more
TL;DR: By parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
Journal ArticleDOI
ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
E. Van Cutsem,Andrés Cervantes,René Adam,Alberto Sobrero,J.H.J.M. van Krieken,Dan Aderka,E. Aranda Aguilar,Alberto Bardelli,Al B. Benson,György Bodoky,Fortunato Ciardiello,André D'Hoore,Eduardo Díaz-Rubio,J.-Y. Douillard,Michel Ducreux,Alfredo Falcone,Axel Grothey,Thomas Gruenberger,Karin Haustermans,Volker Heinemann,Paulo M. Hoff,C.-H. Köhne,R. Labianca,Pierre Laurent-Puig,Brigette B.Y. Ma,Tim Maughan,Kei Muro,Nicola Normanno,Pia Österlund,Pia Österlund,Wim J.G. Oyen,Demetris Papamichael,George Pentheroudakis,Per Pfeiffer,Timothy J. Price,C.J.A. Punt,Jens Ricke,Arnaud Roth,R. Salazar,Werner Scheithauer,H.-J. Schmoll,Josep Tabernero,Julien Taieb,Sabine Tejpar,Harpreet Wasan,Takayuki Yoshino,Aziz Zaanan,Dirk Arnold +47 more
TL;DR: These ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
Journal ArticleDOI
Wnt signaling in cancer.
TL;DR: Current insights into novel components of Wnt pathways are reviewed and how Wnt signaling affects maintenance of cancer stem cells, metastasis and immune control are described.
Journal ArticleDOI
A framework for advancing our understanding of cancer-associated fibroblasts
Erik Sahai,Igor Astsaturov,Edna Cukierman,David G. DeNardo,Mikala Egeblad,Ronald M. Evans,Ronald M. Evans,Douglas T. Fearon,Douglas T. Fearon,Florian R. Greten,Sunil R. Hingorani,Tony Hunter,Richard O. Hynes,Rakesh K. Jain,Tobias Janowitz,Claus Jørgensen,Alec C. Kimmelman,Mikhail G. Kolonin,Robert G. Maki,Robert G. Maki,R. Scott Powers,Ellen Puré,Daniel C. Ramirez,Ruth Scherz-Shouval,Mara H. Sherman,Sheila A. Stewart,Thea D. Tlsty,David A. Tuveson,Fiona M. Watt,Valerie M. Weaver,Ashani T. Weeraratna,Zena Werb +31 more
TL;DR: This Consensus Statement issues a call to action for all cancer researchers to standardize assays and report metadata in studies of cancer-associated fibroblasts to advance the understanding of this important cell type in the tumour microenvironment.
Journal ArticleDOI
The immune contexture in cancer prognosis and treatment
Wolf H. Fridman,Laurence Zitvogel,Catherine Sautès-Fridman,Catherine Sautès-Fridman,Catherine Sautès-Fridman,Guido Kroemer +5 more
TL;DR: The immune contexture, which is determined by the density, composition, functional state and organization of the leukocyte infiltrate of the tumour, can yield information that is relevant to prognosis, prediction of a treatment response and various other pharmacodynamic parameters.
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