Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia
Tea Pemovska,Mika Kontro,Bhagwan Yadav,Henrik Edgren,Samuli Eldfors,Agnieszka Szwajda,Henrikki Almusa,Maxim M. Bespalov,Pekka Ellonen,Erkki Elonen,Bjørn Tore Gjertsen,Riikka Karjalainen,Evgeny Kulesskiy,Sonja Lagström,Anna Lehto,Maija Lepistö,Tuija Lundán,Muntasir Mamun Majumder,Jesus M. Lopez Marti,Pirkko Mattila,Astrid Murumägi,Satu Mustjoki,Aino Palva,Alun Parsons,Tero Pirttinen,Maria E. Rämet,Minna Suvela,Laura Turunen,Imre Vastrik,Maija Wolf,Jonathan Knowles,Tero Aittokallio,Caroline A. Heckman,Kimmo Porkka,Olli Kallioniemi,Krister Wennerberg +35 more
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TLDR
An ISM strategy to optimize safe and effective personalized cancer therapies for individual patients as well as to understand and predict disease evolution and the next line of therapy could facilitate systematic drug repositioning of approved targeted drugs.Abstract:
We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profiling and ex vivo drug sensitivity and resistance testing (DSRT) of patients9 cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered five major taxonomic drug-response subtypes based on DSRT profiles, some with distinct genomic features (e.g., MLL gene fusions in subgroup IV and FLT3 -ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. After progression under DSRT-guided therapies, AML cells displayed significant clonal evolution and novel genomic changes potentially explaining resistance, whereas ex vivo DSRT data showed resistance to the clinically applied drugs and new vulnerabilities to previously ineffective drugs. Significance: Here, we demonstrate an ISM strategy to optimize safe and effective personalized cancer therapies for individual patients as well as to understand and predict disease evolution and the next line of therapy. This approach could facilitate systematic drug repositioning of approved targeted drugs as well as help to prioritize and de-risk emerging drugs for clinical testing. Cancer Discov; 3(12); 1416–29. ©2013 AACR. See related commentary by Hourigan and Karp, p. 1336 This article is highlighted in the In This Issue feature, p. 1317read more
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Precision medicine for cancer with next-generation functional diagnostics
TL;DR: A future diagnostic strategy that integrates functional testing with next-generation sequencing and immunoprofiling to precisely match combination therapies to individual cancer patients is suggested.
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A survey of current trends in computational drug repositioning
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Screening out irrelevant cell-based models of disease
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TL;DR: In this article, the authors propose a set of principles to facilitate the definition and development of disease-relevant assays, and discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery.
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In silico prescription of anticancer drugs to cohorts of 28 tumor types reveals targeting opportunities.
Carlota Rubio-Perez,David Tamborero,Michael P Schroeder,Albert A. Antolin,Jordi Deu-Pons,Christian Perez-Llamas,Jordi Mestres,Abel Gonzalez-Perez,Nuria Lopez-Bigas,Nuria Lopez-Bigas +9 more
TL;DR: A comprehensive assessment of the scope of targeted therapeutic agents in a large pan-cancer cohort and an in silico prescription strategy based on identification of the driver alterations in each tumor and their druggability options is developed.
References
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Book
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
TL;DR: Thank you very much for reading who classification of tumours of haematopoietic and lymphoid tissues, and maybe you have knowledge that, people have look hundreds of times for their chosen readings like this, but end up in malicious downloads.
Journal ArticleDOI
A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3
Pablo Cingolani,Adrian E. Platts,Le Lily Wang,M. Coon,Tung T. Nguyen,Luan Wang,Susan Land,Xiangyi Lu,Douglas M. Ruden +8 more
TL;DR: It appears that the 5′ and 3′ UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus.
Journal ArticleDOI
VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing
Daniel C. Koboldt,Qunyuan Zhang,David E. Larson,Dong Shen,Michael D. McLellan,Ling Lin,Christopher A. Miller,Elaine R. Mardis,Li Ding,Richard K. Wilson +9 more
TL;DR: An analysis tool for the detection of somatic mutations and copy number alterations in exome data from tumor-normal pairs is presented and new light is shed on the landscape of genetic alterations in ovarian cancer.
Journal ArticleDOI
Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia
Timothy J. Ley,Christopher A. Miller,Li Ding,Benjamin J. Raphael,Andrew J. Mungall,Gordon Robertson,Katherine A. Hoadley,Timothy J. Triche,Peter W. Laird,Jack Baty,Lucinda Fulton,Robert S. Fulton,Sharon Heath,Joelle Kalicki-Veizer,Cyriac Kandoth,Jeffery M. Klco,Daniel C. Koboldt,Krishna L. Kanchi,Shashikant Kulkarni,Tamara Lamprecht,David E. Larson,G. Lin,Charles Lu,Michael D. McLellan,Joshua F. McMichael,Jacqueline E. Payton,Heather Schmidt,David H. Spencer,Michael H. Tomasson,John W. Wallis,Lukas D. Wartman,Mark A. Watson,John S. Welch,Michael C. Wendl,Adrian Ally,Miruna Balasundaram,Inanc Birol,Yaron S.N. Butterfield,Readman Chiu,Andy Chu,Eric Chuah,Hye Jung E. Chun,Richard Corbett,Noreen Dhalla,Ranabir Guin,An He,Carrie Hirst,Martin Hirst,Robert A. Holt,Steven J.M. Jones,Aly Karsan,Darlene Lee,Haiyan I. Li,Marco A. Marra,Michael Mayo,Richard A. Moore,Karen Mungall,Jeremy Parker,Erin Pleasance,Patrick Plettner,Jacquie Schein,Dominik Stoll,Lucas Swanson,Angela Tam,Nina Thiessen,Richard Varhol,Natasja Wye,Yongjun Zhao,Stacey Gabriel,Gad Getz,Carrie Sougnez,Lihua Zou,Mark D.M. Leiserson,Fabio Vandin,Hsin-Ta Wu,Frederick Applebaum,Stephen B. Baylin,Rehan Akbani,Bradley M. Broom,Ken Chen,Thomas C. Motter,Khanh Thi-Thuy Nguyen,John N. Weinstein,Nianziang Zhang,Martin L. Ferguson,Christopher Adams,Aaron D. Black,Jay Bowen,Julie M. Gastier-Foster,Thomas Grossman,Tara M. Lichtenberg,Lisa Wise,Tanja Davidsen,John A. Demchok,Kenna R. Mills Shaw,Margi Sheth,Heidi J. Sofia,Liming Yang,James R. Downing,Greg Eley,Shelley Alonso,Brenda Ayala,Julien Baboud,Mark Backus,Sean P. Barletta,Dominique L. Berton,Anna L. Chu,Stanley Girshik,Mark A. Jensen,Ari B. Kahn,Prachi Kothiyal,Matthew C. Nicholls,Todd Pihl,David Pot,Rohini Raman,Rashmi N. Sanbhadti,Eric E. Snyder,Deepak Srinivasan,Jessica Walton,Yunhu Wan,Zhining Wang,Jean Pierre J. Issa,Michelle M. Le Beau,Martin Carroll,Hagop M. Kantarjian,Steven M. Kornblau,Moiz S. Bootwalla,Phillip H. Lai,Hui Shen,David Van Den Berg,Daniel J. Weisenberger,Daniel C. Link,Matthew J. Walter,Bradley A. Ozenberger,Elaine R. Mardis,Peter Westervelt,Timothy A. Graubert,John F. DiPersio,Richard K. Wilson +138 more
TL;DR: It is found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients and the databases from this study are widely available to serve as a foundation for further investigations of AMl pathogenesis, classification, and risk stratification.
Journal ArticleDOI
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet.
Hartmut Döhner,Elihu H. Estey,Sergio Amadori,Frederick R. Appelbaum,Thomas Büchner,Alan Kenneth Burnett,Hervé Dombret,Pierre Fenaux,David Grimwade,Richard A. Larson,Francesco Lo-Coco,Tomoki Naoe,Dietger Niederwieser,Gert J. Ossenkoppele,Miguel A. Sanz,Jorge Sierra,Martin S. Tallman,Bob Löwenberg,Clara D. Bloomfield +18 more
TL;DR: An international expert panel is provided to provide updated evidence- and expert opinion-based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials.
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