The future of epigenetic therapy in solid tumours--lessons from the past.
TLDR
It is hypothesized that in using low-dose epigenetic-modulating agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic and off-target effect observed at high dose, and could give these agents a prominent place in cancer management.Abstract:
The promise of targeting epigenetic abnormalities for cancer therapy has not been realized for solid tumours, although increasing evidence is demonstrating its worth in haematological malignancies. In fact, true clinical efficacy in haematopoietic-related neoplasms has only become evident at low doses of epigenetic-targeting drugs (namely, inhibitors of histone deacetylase and DNA methyltransferases). Describing data from preclinical studies and early clinical trial results, we hypothesize that in using low-dose epigenetic-modulating agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic and off-target effect observed at high dose. We suggest that such optimization of drug dosing and scheduling of currently available agents could give these agents a prominent place in cancer management--when used alone or in combination with other therapies. If so, optimal use of these known agents might also pave the way for the introduction of other agents that target the epigenome.read more
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A cancerous web: signaling, metabolism, and the epigenome.
TL;DR: The recent findings that oncogenic AKT1 activation regulates histone acetylation levels in tumors through regulation of acetyl-CoA metabolism are discussed.
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Theoretical cross-comparative analysis on dynamics of small intestine and colon crypts during cancer initiation
TL;DR: A computational model has been developed to describe the dynamics and structure of human intestinal crypts and to perform a comparative analysis on aberrant DNA methylation level induced in these during cancer initiation and the effect of a set of potential inhibitors with respect to methylation modification in intestinal tissue during initiation of disease.
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Genome-wide screening of abberant methylated drivers combined with relative risk loci in bladder cancer.
TL;DR: To explore important methylation‐driven genes (MDGs) and risk loci to construct risk model for prognosis of bladder cancer (BCa).
Journal ArticleDOI
RNF135 Promoter Methylation Is Associated With Immune Infiltration and Prognosis in Hepatocellular Carcinoma
Xiao Yan Wang,Meng-ke Chen,Xiong Liang,Yu Bai,Ju deng Zeng,Xiao-yi Xu,Hao Li,Jing Wang,Keyu Fan,Guijun Zhao +9 more
TL;DR: Survival analysis disclosed that RNF135 hypermethylation is independently associated with poor clinical outcomes in HCC and associated with prognosis of HCC.
Journal ArticleDOI
Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment
TL;DR: In this article , the authors summarize the recent advances in pancreatic ductal adenocarcinoma biology, biomarker development and therapeutic options from an epigenetic perspective, and provide an overview of clinical trials assessing epigenetically targeted treatments alone or in combination with other anticancer therapies to improve outcomes of patients with PDAC.
References
More filters
Journal ArticleDOI
Hallmarks of cancer: the next generation.
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI
The hallmarks of cancer.
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
Journal ArticleDOI
Chromatin Modifications and Their Function
TL;DR: The surface of nucleosomes is studded with a multiplicity of modifications that can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA.
Journal ArticleDOI
Comprehensive molecular portraits of human breast tumours
Daniel C. Koboldt,Robert S. Fulton,Michael D. McLellan,Heather Schmidt,Joelle Kalicki-Veizer,Joshua F. McMichael,Lucinda Fulton,David J. Dooling,Li Ding,Elaine R. Mardis,Richard K. Wilson,Adrian Ally,Miruna Balasundaram,Yaron S.N. Butterfield,Rebecca Carlsen,Candace Carter,Andy Chu,Eric Chuah,Hye Jung E. Chun,Robin J.N. Coope,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Martin Hirst,Robert A. Holt,Darlene Lee,Haiyan I. Li,Michael Mayo,Richard A. Moore,Andrew J. Mungall,Erin Pleasance,A. Gordon Robertson,Jacqueline E. Schein,Arash Shafiei,Payal Sipahimalani,Jared R. Slobodan,Dominik Stoll,Angela Tam,Nina Thiessen,Richard Varhol,Natasja Wye,Thomas Zeng,Yongjun Zhao,Inanc Birol,Steven J.M. Jones,Marco A. Marra,Andrew D. Cherniack,Gordon Saksena,Gordon Saksena,Robert C. Onofrio,Nam H. Pho,Scott L. Carter,Steven E. Schumacher,Steven E. Schumacher,Barbara Tabak,Barbara Tabak,Bryan Hernandez,Jeff Gentry,Huy Nguyen,Andrew Crenshaw,Kristin G. Ardlie,Rameen Beroukhim,Rameen Beroukhim,Wendy Winckler,Gad Getz,Gad Getz,Stacey Gabriel,Matthew Meyerson,Matthew Meyerson,Lynda Chin,Lynda Chin,Raju Kucherlapati,Katherine A. Hoadley,J. Todd Auman,Cheng Fan,Yidi J. Turman,Yan Shi,Ling Li,Michael D. Topal,Xiaping He,Hann Hsiang Chao,Aleix Prat,Grace O. Silva,Michael D. Iglesia,Wei Zhao,Jerry Usary,Jonathan S. Berg,Michael C. Adams,Jessica K. Booker,Junyuan Wu,Anisha Gulabani,Tom Bodenheimer,Alan P. Hoyle,Janae V. Simons,Matthew G. Soloway,Lisle E. Mose,Stuart R. Jefferys,Saianand Balu,Joel S. Parker,D. Neil Hayes,Charles M. Perou,Simeen Malik,Swapna Mahurkar,Hui Shen,Daniel J. Weisenberger,Timothy J. Triche,Phillip H. Lai,Moiz S. Bootwalla,Dennis T. Maglinte,Benjamin P. Berman,David Van Den Berg,Stephen B. Baylin,Peter W. Laird,Chad J. Creighton,Lawrence A. Donehower,Michael S. Noble,Doug Voet,Nils Gehlenborg,Daniel Di Cara,Juinhua Zhang,Hailei Zhang,Chang-Jiun Wu,Spring Yingchun Liu,Michael S. Lawrence,Lihua Zou,Andrey Sivachenko,Pei Lin,Petar Stojanov,Rui Jing,Juok Cho,Raktim Sinha,Richard W. Park,Marc Danie Nazaire,James A. Robinson,Helga Thorvaldsdottir,Jill P. Mesirov,Peter J. Park,Sheila Reynolds,Richard Kreisberg,Brady Bernard,Ryan Bressler,Timo Erkkilä,Jake Lin,Vesteinn Thorsson,Wei Zhang,Ilya Shmulevich,Giovanni Ciriello,Nils Weinhold,Nikolaus Schultz,Jianjiong Gao,Ethan Cerami,Benjamin Gross,Anders Jacobsen,Rileen Sinha,B. Arman Aksoy,Yevgeniy Antipin,Boris Reva,Ronglai Shen,Barry S. Taylor,Marc Ladanyi,Chris Sander,Pavana Anur,Paul T. Spellman,Yiling Lu,Wenbin Liu,Roel R.G. Verhaak,Gordon B. Mills,Gordon B. Mills,Rehan Akbani,Nianxiang Zhang,Bradley M. Broom,Tod D. Casasent,Chris Wakefield,Anna K. Unruh,Keith A. Baggerly,Kevin R. Coombes,John N. Weinstein,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Evan O. Paull,Daniel E. Carlin,Christopher K. Wong,Artem Sokolov,Janita Thusberg,Sean D. Mooney,Sam Ng,Theodore C. Goldstein,Kyle Ellrott,Mia Grifford,Christopher Wilks,Singer Ma,Brian Craft,Chunhua Yan,Ying Hu,Daoud Meerzaman,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Jay Bowen,Nilsa C. Ramirez,Nilsa C. Ramirez,Aaron D. Black,Robert E. Pyatt,Robert E. Pyatt,Peter White,Peter White,Erik Zmuda,Jessica Frick,Tara M. Lichtenberg,Robin Brookens,Myra M. George,Mark Gerken,Hollie A. Harper,Kristen M. Leraas,Lisa Wise,Teresa R. Tabler,Cynthia McAllister,Thomas Barr,Melissa Hart-Kothari,Katie Tarvin,Charles Saller,George E. Sandusky,Colleen Mitchell,Mary Iacocca,Jennifer Brown,Brenda Rabeno,Christine Czerwinski,Nicholas J. Petrelli,Oleg Dolzhansky,Mikhail Abramov,Olga Voronina,Olga Potapova,Jeffrey R. Marks,Wiktoria Maria Suchorska,Dawid Murawa,Witold Kycler,Matthew Ibbs,Konstanty Korski,Arkadiusz Spychała,Pawel Murawa,Jacek J. Brzeziński,Hanna Perz,Radoslaw Łaźniak,M. Teresiak,Honorata Tatka,Ewa Leporowska,Marta Bogusz-Czerniewicz,Julian Malicki,Andrzej Mackiewicz,Maciej Wiznerowicz,Xuan Van Le,Bernard Kohl,Nguyen Viet Tien,Richard Thorp,Nguyen Van Bang,Howard H. Sussman,Bui Duc Phu,Richard A. Hajek,Nguyen Phi Hung,Huynh Quyet Thang,Khurram Z. Khan,Robert Penny,David Mallery,Erin Curley,Candace Shelton,Peggy Yena,James N. Ingle,Fergus J. Couch,Wilma L. Lingle,Tari A. King,Ana M. Gonzalez-Angulo,Ana M. Gonzalez-Angulo,Mary D. Dyer,Shuying Liu,Xiaolong Meng,Modesto Patangan,Frederic Waldman,Frederic Waldman,Hubert Stoppler,W. Kimryn Rathmell,Leigh B. Thorne,Mei Huang,Lori Boice,Ashley Hill,Carl Morrison,Carmelo Gaudioso,Wiam Bshara,Kelly Daily,Sophie C. Egea,Mark D. Pegram,Carmen Gomez-Fernandez,Rajiv Dhir,Rohit Bhargava,Adam Brufsky,Craig D. Shriver,Jeffrey A. Hooke,Jamie Leigh Campbell,Richard J. Mural,Hai Hu,Stella Somiari,Caroline Larson,Brenda Deyarmin,Leonid Kvecher,Albert J. Kovatich,Matthew J. Ellis,Thomas Stricker,Kevin P. White,Olufunmilayo I. Olopade,Chunqing Luo,Yaqin Chen,Ron Bose,Li-Wei Chang,Andrew H. Beck,Todd Pihl,Mark A. Jensen,Robert Sfeir,Ari B. Kahn,Anna Chu,Prachi Kothiyal,Zhining Wang,Eric E. Snyder,Joan Pontius,Brenda Ayala,Mark Backus,Jessica Walton,Julien Baboud,Dominique L. Berton,Matthew C. Nicholls,Deepak Srinivasan,Rohini Raman,Stanley Girshik,Peter A. Kigonya,Shelley Alonso,Rashmi N. Sanbhadti,Sean P. Barletta,David Pot,Margi Sheth,John A. Demchok,Kenna R. Mills Shaw,Liming Yang,Greg Eley,Martin L. Ferguson,Roy Tarnuzzer,Jiashan Zhang,Laura A.L. Dillon,Kenneth H. Buetow,Peter Fielding,Bradley A. Ozenberger,Mark S. Guyer,Heidi J. Sofia,Jacqueline D. Palchik +355 more
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
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