PURPOSE OF REVIEW: The purpose of this review is to provide an overview of recent advances in the development of histone deacetylase inhibitors (HDACi) for the treatment of cancer. RECENT FINDINGS: Recently, there has been a dramatic expansion of HDACi clinical investigation. There are now 11 HDACi in clinical trial, including inhibitors with a broad spectrum of HDAC isoform inhibitory activity as well as drugs with isoform selectivity. Over 70 combination therapy trials are in progress. Major areas of progress covered include the entry of new HDAC inhibitors into clinical development, recent progress in understanding of molecular mechanisms of HDACi anticancer activity, and a preclinical and clinical update on HDACi in combination. SUMMARY: In the period under review there have been advances in understanding of HDACi mechanisms of action, identification of rational combinations that address increased efficacy and overcoming resistance, and greatly expanded clinical development of pan-HDAC-inhibitory and isoform-selective inhibitors in monotherapy and combination therapy protocols.
PURPOSE OF REVIEW: The purpose of this review is to provide an overview of recent advances in the development of histone deacetylase inhibitors (HDACi) for the treatment of cancer. RECENT FINDINGS: Recently, there has been a dramatic expansion of HDACi clinical investigation. There are now 11 HDACi in clinical trial, including inhibitors with a broad spectrum of HDAC isoform inhibitory activity as well as drugs with isoform selectivity. Over 70 combination therapy trials are in progress. Major areas of progress covered include the entry of new HDAC inhibitors into clinical development, recent progress in understanding of molecular mechanisms of HDACi anticancer activity, and a preclinical and clinical update on HDACi in combination. SUMMARY: In the period under review there have been advances in understanding of HDACi mechanisms of action, identification of rational combinations that address increased efficacy and overcoming resistance, and greatly expanded clinical development of pan-HDAC-inhibitory and isoform-selective inhibitors in monotherapy and combination therapy protocols.
Authors: Yukihiko Kato; Kiyoshi Yoshimura; Tahiro Shin; Henk Verheul; Hans Hammers; Tolib B Sanni; Brenda C Salumbides; Karen Van Erp; Richard Schulick; Roberto Pili Journal: Clin Cancer Res Date: 2007-08-01 Impact factor: 12.531
Authors: Guillermo Garcia-Manero; Sarit Assouline; Jorge Cortes; Zeev Estrov; Hagop Kantarjian; Hui Yang; Willie M Newsome; Wilson H Miller; Caroline Rousseau; Ann Kalita; Claire Bonfils; Marja Dubay; Tracy-Ann Patterson; Zuomei Li; Jeffrey M Besterman; Gregory Reid; Eric Laille; Robert E Martell; Mark Minden Journal: Blood Date: 2008-05-21 Impact factor: 22.113
Authors: Suresh S Ramalingam; Robert A Parise; Ramesh K Ramanathan; Ramesh K Ramananthan; Theodore F Lagattuta; Lori A Musguire; Ronald G Stoller; Douglas M Potter; Athanassios E Argiris; James A Zwiebel; Merrill J Egorin; Chandra P Belani Journal: Clin Cancer Res Date: 2007-05-17 Impact factor: 12.531
Authors: J Arts; P Angibaud; A Mariën; W Floren; B Janssens; P King; J van Dun; L Janssen; T Geerts; R W Tuman; D L Johnson; L Andries; M Jung; M Janicot; K van Emelen Journal: Br J Cancer Date: 2007-11-13 Impact factor: 7.640
Authors: Fredika M Robertson; Wendy A Woodward; Ross Pickei; Zaiming Ye; William Bornmann; Ashutosh Pal; Zhenghong Peng; Carolyn S Hall; Massimo Cristofanilli Journal: Cancer Date: 2010-06-01 Impact factor: 6.860
Authors: Seung Hyun Oh; Young Mi Whang; Hye-Young Min; Seung Ho Han; Ju-Hee Kang; Ki-Hoon Song; Bonnie S Glisson; Yeul Hong Kim; Ho-Young Lee Journal: Int J Cancer Date: 2012-03-28 Impact factor: 7.396
Authors: C Blattmann; S Oertel; M Thiemann; K J Weber; P Schmezer; O Zelezny; R Lopez Perez; A E Kulozik; J Debus; V Ehemann Journal: Strahlenther Onkol Date: 2012-01-18 Impact factor: 3.621
Authors: David M Lucas; Lapo Alinari; Derek A West; Melanie E Davis; Ryan B Edwards; Amy J Johnson; Kristie A Blum; Craig C Hofmeister; Michael A Freitas; Mark R Parthun; Dasheng Wang; Amy Lehman; Xiaoli Zhang; David Jarjoura; Samuel K Kulp; Carlo M Croce; Michael R Grever; Ching-Shih Chen; Robert A Baiocchi; John C Byrd Journal: PLoS One Date: 2010-06-03 Impact factor: 3.240
Authors: Rosalind A Eeles; Zsofia Kote-Jarai; Ali Amin Al Olama; Graham G Giles; Michelle Guy; Gianluca Severi; Kenneth Muir; John L Hopper; Brian E Henderson; Christopher A Haiman; Johanna Schleutker; Freddie C Hamdy; David E Neal; Jenny L Donovan; Janet L Stanford; Elaine A Ostrander; Sue A Ingles; Esther M John; Stephen N Thibodeau; Daniel Schaid; Jong Y Park; Amanda Spurdle; Judith Clements; Joanne L Dickinson; Christiane Maier; Walther Vogel; Thilo Dörk; Timothy R Rebbeck; Kathleen A Cooney; Lisa Cannon-Albright; Pierre O Chappuis; Pierre Hutter; Maurice Zeegers; Radka Kaneva; Hong-Wei Zhang; Yong-Jie Lu; William D Foulkes; Dallas R English; Daniel A Leongamornlert; Malgorzata Tymrakiewicz; Jonathan Morrison; Audrey T Ardern-Jones; Amanda L Hall; Lynne T O'Brien; Rosemary A Wilkinson; Edward J Saunders; Elizabeth C Page; Emma J Sawyer; Stephen M Edwards; David P Dearnaley; Alan Horwich; Robert A Huddart; Vincent S Khoo; Christopher C Parker; Nicholas Van As; Christopher J Woodhouse; Alan Thompson; Tim Christmas; Chris Ogden; Colin S Cooper; Melissa C Southey; Artitaya Lophatananon; Jo-Fen Liu; Laurence N Kolonel; Loic Le Marchand; Tiina Wahlfors; Teuvo L Tammela; Anssi Auvinen; Sarah J Lewis; Angela Cox; Liesel M FitzGerald; Joseph S Koopmeiners; Danielle M Karyadi; Erika M Kwon; Mariana C Stern; Roman Corral; Amit D Joshi; Ahva Shahabi; Shannon K McDonnell; Thomas A Sellers; Julio Pow-Sang; Suzanne Chambers; Joanne Aitken; R A Frank Gardiner; Jyotsna Batra; Mary Anne Kedda; Felicity Lose; Andrea Polanowski; Briony Patterson; Jürgen Serth; Andreas Meyer; Manuel Luedeke; Klara Stefflova; Anna M Ray; Ethan M Lange; Jim Farnham; Humera Khan; Chavdar Slavov; Atanaska Mitkova; Guangwen Cao; Douglas F Easton Journal: Nat Genet Date: 2009-09-20 Impact factor: 38.330