Paterson Institute for Cancer Research

Manchester, United Kingdom

Paterson Institute for Cancer Research

Manchester, United Kingdom
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News Article | December 20, 2016

Dublin, Dec. 20, 2016 (GLOBE NEWSWIRE) -- Research and Markets has announced the addition of the "HDAC Inhibitors Market, 2016 - 2026" report to their offering. The HDAC Inhibitors Market, 2016-2026 report was commissioned to examine the current landscape and the future outlook of the growing pipeline of products in this area. HDACs have been studied in cellular processes such as apoptosis, autophagy, metabolism, DNA damage repair, cell cycle control and senescence. Altered expression of HDACs has been observed in different tumors; this makes them a potential target for treatment of cancer and other genetic or epigenetic related disorders. Inhibition of HDACs has shown positive results in disruption of multiple cell signaling pathways and prevention of tumor growth. The study provides a detailed market forecast and opportunity analysis for the time period 2016-2026. The research, analysis and insights presented in this report include potential sales of the approved drugs and the ones in late stages of development (phase III and phase II). To add robustness to our model, we have provided three scenarios for our market forecast; these include the conservative, base and optimistic scenarios. Our opinions and insights, presented in this study were influenced by several discussions we conducted with experts in this area. All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified. Example Highlights - Nearly 90 HDAC inhibitors are currently in clinical / preclinical stages of development; the clinical molecules account for over 30% of the pipeline while over 60% is captured by molecules in the preclinical / discovery stage. - With 66% of the pipeline molecules targeting oncological indications, cancer remains one of the most widely studied field for HDAC inhibitors. Within oncology, hematological malignancies such as PTCL and CTCL are popular targets; three HDAC inhibitors (Zolinza, ISTODAX® and BELEODAQ®) are approved for these indications. Other therapeutic areas such as autoimmune disorders, infectious diseases, inflammatory disorders, neurological disorders, are also gradually gaining traction. - Although the market was initially led by the large-size pharma players (such as Celgene, Merck, Novartis), the current market is characterized by the presence of several small / mid-sized pharma players. Notable examples of the small and mid-sized firms include 4SC, Chroma Therapeutics, CrystalGenomics, Curis, Evgen Pharma, FORUM Pharmaceuticals, Karus Therapeutics, Mirati Therapeutics, MEI Pharma, Shenzhen Chipscreen Biosciences, Syndax Pharmaceuticals and TetraLogic Pharmaceuticals. - In addition, there are several non-industry institutes and universities that are primarily carrying out preclinical research. Examples of these include Harvard Medical School (BG45), Imperial College London (C1A), Kyoto University (Jd, Sd), National Taiwan University (Quinazolin-4-one derivatives), Taipei Medical University (MPT0E028), University of Messina (MC-1575, MC-1568). - Four of the five approved drugs are pan-HDAC inhibitors targeting HDAC isoforms non-specifically. However, in the past few years, several class selective HDAC inhibitors have entered the clinic; these are associated with a higher efficacy and result in decreased toxicity from the treatment. Of the total HDAC inhibitors identified, 52% of the molecules are class specific; of these, 33% molecules target Class I specific isoforms and the rest target Class II specific isoforms of HDACs. Notable examples of molecules targeting class-specific HDACs includeentinostat (phase III), resminostat (phase II), SHP-141 (phase II), mocetinostat (phase II), CHR-3996 (phase I/II) and ricolinostat (phase I/II). - The HDAC inhibitors market is expected to grow at a healthy annual rate of 32% over the next decade.With multiple potential target indications, Istodax® is expected to capture the largest market share (close to 21%) in 2026, followed by entinostat, Farydak® and Beleodaq®. Key Topics Covered: 1. Preface 1.1. Scope Of The Report 1.2. Research Methodology 1.3. Chapter Outlines 2. Executive Summary 3. Introduction 3.1. The Central Dogma of Molecular Biology and Cell Cycle 3.2. DNA: Structure and Functions 3.3. Fundamentals of Epigenetics 3.3.1. Effect of Histone Modification on DNA Based Processes 3.3.2. Chromatin Structure Modification and its Enzymes 3.4. Histone Deacetylases (HDACs) 3.4.1. Classification of HDACs 3.4.2. Role of HDACs and HDAC Inhibitors in Cellular Processes 3.5. HDAC Inhibitors 3.5.1. Structure and Classification 3.5.2. Different Types of HDAC Inhibitors 3.5.3. Therapeutic Applications of HDAC Inhibitors 4. HDAC Inhibitors: Market Landscape 4.1. Chapter Overview 4.2. Development Pipeline of HDAC Inhibitors 4.3. Distribution by Phase of Development 4.4. Distribution by Therapeutic Area 4.5. Distribution by Class Specificity 4.6. Distribution by Type of Developer 4.7. Distribution by Geography 4.8. Active Industry Players 5. Drug Profiles: Marketed And Late-Stage HDAC Inhibitors 5.1. Chapter Overview 5.2. Company and Drug Profiles: Marketed and Phase III Molecules 5.2.1. Celgene Corporation 5.2.3. Novartis 5.2.4. Shenzhen Chipscreen Biosciences 5.2.5. Syndax Pharmaceuticals 5.3. Drug Profiles: Phase II Molecules 5.3.1. Abexinostat (PCI-24781) 5.3.2. CUDC-907 5.3.3. FRM-0334 (EVP-0334) 5.3.4. Givinostat (ITF2357) 5.3.5. Mocetinostat (MGCD103) 5.3.6. Pracinostat (SB939) 5.3.7. Resminostat (4SC-201) 5.3.8. SFX-01 5.3.9. SHAPE (SHP-141) 5.3.10. Tefinostat (CHR-2845) 6. Key Insights: Therapeutic Area, Class Specificity, Clinical Endpoints 6.1. Clinical Development Analysis: Class Specificity and Therapeutic Areas 6.2. Clinical Development Analysis: Developer Landscape 6.3. Clinical Development Analysis: Trial Endpoint Comparison 7. Market Forecast And Opportunity Analysis 7.1. Chapter Overview 7.2. Scope and Limitations 7.3. Forecast Methodology 7.4. Overall HDAC Inhibitors Market 7.5. HDAC Inhibitors Market: Individual Forecasts 7.5.1. Zolinza (Merck) 7.5.2. Istodax® (Celgene Corporation) 7.5.3. Beleodaq® (Onxeo) 7.5.4. Farydak® (Novartis) 7.5.5. Epidaza® (Shenzhen Chipscreen Biosciences) 7.5.6. Entinostat (Syndax Pharmaceuticals) 7.5.7. Abexinostat (Pharmacyclics) 7.5.8. CUDC-907 (Curis) 7.5.9. FRM-0334 (FORUM Pharmaceuticals) 7.5.10. Mocetinostat (Mirati Therapeutics) 7.5.11. Pracinostat (MEI Pharma) 7.5.12. Resminostat (4SC, Menarini, Yakult Honsha) 7.5.13. SFX-01 (Evgen Pharma) 7.5.14. SHP-141 (TetraLogic Pharmaceuticals) 7.5.15. Tefinostat (Chroma Therapeutics) 8. Publication Analysis 8.1. Chapter Overview 8.2. HDAC Inhibitors: Publications 8.3. Publication Analysis: Quarterly Distribution 8.4. Publication Analysis: Distribution by HDAC Inhibitor Class 8.5. Publication Analysis: Distribution by Drugs Studied 8.6. Publication Analysis: Distribution by Therapeutic Area 8.7. Publication Analysis: Distribution by Journals 8.8. Publication Analysis: Distribution by Phase of Development 8.9. Publication Analysis: Distribution by Type of Therapy 9. Social Media: Emerging Trends 9.1. Chapter Overview 9.1.1. Trends on Twitter 9.1.2. Trends on Facebook 10. Conclusion 10.1. The Pipeline is Healthy with Several Molecules in Preclinical Stages of Development 10.2. HDAC Inhibitors Cater to a Wide Spectrum of Disease Areas 10.3. Class Specific HDAC Inhibitors Have Been Explored for a More Targeted Approach 10.4. The Interest is Gradually Rising Amongst Both Industry and Non-Industry Players 10.5. Supported by a Robust Preclinical Pipeline, HDAC Inhibitors are Expected to Emerge as A Multi-Billion Dollar Market 11. Interview Transcripts 11.1. Chapter Overview 11.2. Dr. Simon Kerry, CEO, Karus Therapeutics 11.3. Dr. James Christensen, CSO and Senior VP, Mirati Therapeutics 11.4. Dr. Hyung J. Chun, MD, FAHA, Associate Professor of Medicine, Yale School of Medicine 12. Appendix 1: Tabulated Data 13. Appendix 2: List Of Companies And Organizations Companies Mentioned - 4SC - AACR - AbbVie - Acceleron Pharma - Acetylon Pharmaceuticals - Active Biotech - Agios Pharmaceuticals - ASH - Arno Therapeutics - Astellas Pharma - Bayer Schering Pharma - Baylor College of Medicine - BioMarin - Bionor Immuno - bluebird bio - Case Comprehensive Cancer Center - Celera Genomics - Celgene - Celleron Therapeutics - Centre de Recherche en Cancérologie - CETYA Therapeutics - CHDI Foundation - Chipscreen Biosciences - Chong Kun Dang Pharmaceutical - Chroma Therapeutics - Croix-Rousse Hospital - CrystalGenomics - Curis - DAC - Diaxonhit - DNA Therapeutics - Duke University - ECOG-ACRIN Cancer Research Group - Eddingpharm - Eisai - Epizyme - Errant Gene Therapeutics - European Calcified Tissue Society - Evgen Pharma - FORMA Therapeutics - FORUM Pharmaceuticals - Fudan University - Genentech - Genextra - Gilead - Gloucester Pharmaceuticals - GNT Biotech - GSK - Harvard Medical School - Henan Cancer Hospital - HUYA Biosciences - Ikerchem - Imperial College London - In2Gen - International Bone and Mineral Society - Israel Cancer Association and Bar Ilan University - Italfarmaco - Johnson and Johnson - Kalypsys - Karus Therapeutics - King's College, University of London - Kyoto Prefectural University of Medicine - Kyoto University - Kyowa Hakko Kirin - Leukemia and Lymphoma Society - Lymphoma Academic Research Organization - Massachusetts General Hospital - Mayo Clinic - MedImmune - MEI Pharma - Memorial Sloan-Kettering Cancer Center - Menarini - Merck - MethylGene - Mirati Therapeutics - Morphosys - Mundipharma-EDO - National Brain Research Centre - National Comprehensive Cancer Network - National Taiwan University - NCI - Novartis - NuPotential - Oceanyx Pharma - Oncolys Biopharma - Onxeo - Onyx - Orchid Pharma - Paterson Institute for Cancer Research - Pfizer - Pharmacyclics - Pharmion Corporation - Quimatryx - Quintiles - Repligen - Respiratorius - Roche - Rodin Therapeutics - Royal Veterinary College, University of London - Ruijin Hospital - S*Bio - Sarcoma Alliance for Research through Collaboration - Seattle Genetics - Servier Canada - Shape Pharmaceuticals - Sidney Kimmel Comprehensive Cancer Center - Sigma Tau Pharmaceuticals - Signal Rx - SpeBio - Spectrum Pharmaceuticals - Stanley Center for Psychiatric Research - Sutro Biopharma - Syndax Pharmaceuticals - Synovo GmbH - Taipei Medical University - TetraLogic Pharmaceuticals - University of Liverpool - University of Messina - University of Miami - Vanderbilt University School of Medicine - Ventana Medical Systems - Vilnius University - Yakult Honsha - Yale University - Yonsei University College of Medicine For more information about this report visit

Lu P.,Paterson Institute for Cancer Research | Lu P.,University of California at San Francisco | Takai K.,University of California at San Francisco | Weaver V.M.,University of California at San Francisco | Werb Z.,University of California at San Francisco
Cold Spring Harbor Perspectives in Biology | Year: 2011

The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine. © 2011 Cold Spring Harbor Laboratory Press. all rights reserved.

Pines J.,Gurdon Institute | Hagan I.,Paterson Institute for Cancer Research
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

Orson Welles might have been a little unfair on the Swiss, after all cuckoo clocks were developed in the Schwartzwald, but, more importantly, Swiss democracy gives remarkably stable government with considerable decision-making at the local level. The alternative is the battling city-states of Renaissance Italy: culturally rich but chaotic at a higher level of organization. As our understanding of the cell cycle improves, it appears that the cell is organized more along the lines of Switzerland than Renaissance Italy, and one major challenge is to determine how local decisions are made and coordinated to produce the robust cell cycle mechanisms that we observe in the cell as a whole. © 2011 The Royal Society.

Gozdecka M.,Paterson Institute for Cancer Research | Breitwieser W.,Paterson Institute for Cancer Research
Biochemical Society Transactions | Year: 2012

MAPK (mitogen-activated protein kinase) pathways are among the most frequently deregulated signalling events in cancer. Among the critical targets of MAPK activities are members of the AP-1 (activator protein 1) transcription factor, a dimeric complex consisting of Jun, Fos, Maf and ATF (activating transcription factor) family DNA-binding proteins. Depending on the cellular context, the composition of the dimeric complexes determines the regulation of growth, survival or apoptosis. JNK (c-Jun N-terminal kinase), p38 and a number of Jun and Fos family proteins have been analysed for their involvement in oncogenic transformation and tumour formation. These data are also emerging for the ATF components of the AP-1 factor. The aim of the present review is to provide an overview of the functions of two ATF family proteins, ATF2 and ATF7, in mammalian development and their potential functions in tumour formation. ©The Authors Journal compilation ©2012 Biochemical Society.

Wiseman D.H.,Paterson Institute for Cancer Research | Greystoke B.F.,Paterson Institute for Cancer Research | Somervaille T.C.P.,Paterson Institute for Cancer Research
Oncogene | Year: 2014

Human acute myeloid leukemias (AMLs) are sustained by leukemic stem cells (LSCs) that generate through aberrant differentiation the blast cells that make up the bulk of the malignant clone. LSCs were first identified as rare cells with an immunophenotype shared with normal hematopoietic stem cells (HSCs). However, refinements of xenotransplantation assays, alternative methods of quantitation and syngeneic murine models have all led to an appreciation that LSCs display marked variability in frequency, immunophenotype and differentiation potential, both between and even within leukemias. Insights from next-generation sequencing efforts have dramatically extended understanding of the mutational landscape and clonal organization of AML and have added an additional layer of complexity to the biology of LSCs: a requirement to consider the effect of the various recurrently occurring genetic lesions in AML on the initiation and maintenance of leukemic subclones. Despite these advances, cure rates in AML remain substantially unchanged in recent years. A renewed focus on the biological properties of chemotherapy-resistant LSCs, a cellular entity of prime clinical importance, will be required to develop additional therapeutic strategies to enhance patient outcomes. © 2014 Macmillan Publishers Limited All rights reserved.

Gallagher J.T.,Paterson Institute for Cancer Research
Handbook of Experimental Pharmacology | Year: 2012

Heparan sulphate (HS), discovered in 1948 in heparin by-products, only emerged slowly from the shadow of heparin. Its inauspicious beginning was followed by the gradual realisation that HS was a separate entity with distinctive features. Both HS and heparin follow a common biosynthetic route but while heparin reaches full maturity, HS holds on to some of its youthful traits. The novel design and complex patterning of sulphation in HS enable it fulfil key roles in many, diverse biological processes. © 2012 Springer-Verlag Berlin Heidelberg.

Labib K.,Paterson Institute for Cancer Research | de Piccoli G.,Paterson Institute for Cancer Research
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

Checkpoints were originally identified as signalling pathways that delay mitosis in response to DNA damage or defects in chromosome replication, allowing time for DNA repair to occur. The ATR (ataxia- and rad-related) and ATM (ataxia-mutated) protein kinases are recruited to defective replication forks or to sites of DNA damage, and are thought to initiate the DNA damage response in all eukaryotes. In addition to delaying cell cycle progression, however, the S-phase checkpoint pathway also controls chromosome replication and DNA repair pathways in a highly complex fashion, in order to preserve genome integrity. Much of our understanding of this regulation has come from studies of yeasts, in which the best-characterized targets are the stimulation of ribonucleotide reductase activity by multiple mechanisms, and the inhibition of new initiation events at later origins of DNA replication. In addition, however, the S-phase checkpoint also plays a more enigmatic and apparently critical role in preserving the functional integrity of defective replication forks, by mechanisms that are still understood poorly. This review considers some of the key experiments that have led to our current understanding of this highly complex pathway. © 2011 The Royal Society.

Girotti M.R.,Paterson Institute for Cancer Research | Marais R.,Paterson Institute for Cancer Research
Cancer Discovery | Year: 2013

The promise of personalized medicine is upon us, and in some cancers, targeted therapies are rapidly becoming the mainstay of treatment for selected patients based on their molecular profile. The protein kinase BRAF is a driver oncogene in both thyroid cancer and melanoma, but while drugs that target BRAF and its downstream signaling pathway are effective in melanoma, they are ineffective in thyroid cancer. In this issue of Cancer Discovery, Montero-Conde and colleagues investigate why thyroid cancer is resistant to BRAF inhibitors despite the presence of BRAF mutation. © 2013 American Association for Cancer Research.

Weston R.,Paterson Institute for Cancer Research | Peeters H.,Paterson Institute for Cancer Research | Ahel D.,Paterson Institute for Cancer Research
Genes and Development | Year: 2012

To efficiently duplicate their genomic content, cells must overcome DNA lesions that interfere with processive DNA replication. These lesions may be removed and repaired, rather than just tolerated, to allow continuity of DNA replication on an undamaged DNA template. However, it is unclear how this is achieved at a molecular level. Here we identify a new replication-associated factor, ZRANB3 (zinc finger, RAN-binding domain containing 3), and propose its role in the repair of replication-blocking lesions. ZRANB3 has a unique structure-specific endonuclease activity, which is coupled to ATP hydrolysis. It cleaves branched DNA structures with unusual polarity, generating an accessible 39-OH group in the template of the leading strand. Furthermore, ZRANB3 localizes to DNA replication sites and interacts with the components of the replication machinery. It is recruited to damaged replication forks via multiple mechanisms, which involve interactions with PCNA, K63-polyubiquitin chains, and branched DNA structures. Collectively, our data support a role for ZRANB3 in the replication stress response and suggest new insights into how DNA repair is coordinated with DNA replication to maintain genome stability. © 2012 by Cold Spring Harbor Laboratory Press.

Labib K.,Paterson Institute for Cancer Research
Genes and Development | Year: 2010

Chromosome replication occurs precisely once during the cell cycle of almost all eukaryotic cells, and is a highly complex process that is still understood relatively poorly. Two conserved kinases called Cdc7 (cell division cycle 7) and cyclin-dependent kinase (CDK) are required to establish replication forks during the initiation of chromosome replication, and a key feature of this process is the activation of the replicative DNA helicase in situ at each origin of DNA replication. A series of recent studies has shed new light on the targets of Cdc7 and CDK, indicating that chromosome replication probably initiates by a fundamentally similar mechanism in all eukaryotes. © 2010 by Cold Spring Harbor Laboratory Press.

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