Advances in epigenetic therapeutics with focus on solid tumors

A pilot clinical trial of p53/p16-independent epigenetic therapy for pancreatic ductal adenocarcinoma (PDA).

(2020) Davendra Sohal et al.   JOURNAL OF CLINICAL ONCOLOGY

A phase I study of guadecitabine (SGI-110) plus cisplatin in patients with platinum refractory germ cell tumors.

(2020) Costantine Albany et al.   JOURNAL OF CLINICAL ONCOLOGY

Cytosine methylation of mature microRNAs inhibits their functions and is associated with poor prognosis in glioblastoma multiforme

(2020) Mathilde Cheray et al.   Molecular Cancer

Metabolic Coordination of Cell Fate by α-Ketoglutarate-Dependent Dioxygenases

(2020) Sanjeethan C. Baksh et al.   TRENDS IN CELL BIOLOGY

Double Contrast-Enhanced Ultrasonography in Preoperative T Staging of Gastric Cancer: A Comparison With Endoscopic Ultrasonography

(2019) Liang Wang et al.   Frontiers in Oncology

Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer

(2019) Helai P. Mohammad et al.   NATURE MEDICINE

Clinical pharmacokinetics and pharmacodynamics of ivosidenib, an oral, targeted inhibitor of mutant IDH1, in patients with advanced solid tumors

(2019) Bin Fan et al.   INVESTIGATIONAL NEW DRUGS

A phase I, open label, perioperative study of AG-120 and AG-881 in recurrent IDH1 mutant, low-grade glioma: Results from cohort 1.

(2019) Ingo K. Mellinghoff et al.   JOURNAL OF CLINICAL ONCOLOGY

First-in-human study of AZD5153, a small molecule inhibitor of bromodomain protein 4 (BRD4), in patients (pts) with relapsed/refractory (RR) malignant solid tumor and lymphoma: Preliminary data.

(2019) Judy Sing-Zan Wang et al.   JOURNAL OF CLINICAL ONCOLOGY

Dysregulated N6-methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer

(2019) Tong Liu et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma

(2019) Sarah W. Gordon et al.   AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS

The emerging role of epigenetic therapeutics in immuno-oncology

(2019) Michael J. Topper et al.   Nature Reviews Clinical Oncology

LBA10_PRClarIDHy: A global, phase III, randomized, double-blind study of ivosidenib (IVO) vs placebo in patients with advanced cholangiocarcinoma (CC) with an isocitrate dehydrogenase 1 (IDH1) mutation

(2019) G K Abou-Alfa et al.   ANNALS OF ONCOLOGY

Chemical inhibitors make their RNA epigenetic mark

(2019) Megan Cully   NATURE REVIEWS DRUG DISCOVERY

DNA methyltransferase inhibitors induce a BRCAness phenotype that sensitizes NSCLC to PARP inhibitor and ionizing radiation

(2019) Rachel Abbotts et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia

(2019) Gail J. Roboz et al.   BLOOD

A Phase II Trial of Pembrolizumab and Vorinostat in Recurrent Metastatic Head and Neck Squamous Cell Carcinomas and Salivary Gland Cancer

(2019) Cristina P. Rodriguez et al.   CLINICAL CANCER RESEARCH

Phase II study of CC-486 (oral azacitidine) in previously treated patients with locally advanced or metastatic nasopharyngeal carcinoma

(2019) Ricard Mesia et al.   EUROPEAN JOURNAL OF CANCER

Phase I trial of belinostat with cisplatin and etoposide in advanced solid tumors, with a focus on neuroendocrine and small cell cancers of the lung

(2018) Sanjeeve Balasubramaniam et al.   ANTI-CANCER DRUGS

The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia

(2018) Eytan M. Stein et al.   BLOOD

METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m 6 A Modification

(2018) Hengyou Weng et al.   Cell Stem Cell

Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors

(2018) Jeremy Lewin et al.   JOURNAL OF CLINICAL ONCOLOGY

Multiple functions of m6A RNA methylation in cancer

(2018) Yutian Pan et al.   Journal of Hematology & Oncology

Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML

(2018) Courtney D. DiNardo et al.   NEW ENGLAND JOURNAL OF MEDICINE

IDH1/2 Mutations Predict Shorter Survival in Chondrosarcoma

(2018) Iwona Lugowska et al.   Journal of Cancer

Phase 2, multicenter study of the EZH2 inhibitor tazemetostat as monotherapy in adults with relapsed or refractory (R/R) malignant mesothelioma (MM) with BAP1 inactivation.

(2018) Marjorie Glass Zauderer et al.   JOURNAL OF CLINICAL ONCOLOGY

Mocetinostat for patients with previously treated, locally advanced/metastatic urothelial carcinoma and inactivating alterations of acetyltransferase genes

(2018) Petros Grivas et al.   CANCER

ABOUND.2L+: A randomized phase 2 study of nanoparticle albumin‐bound paclitaxel with or without CC‐486 as second‐line treatment for advanced nonsquamous non‐small cell lung cancer (NSCLC)

(2018) Daniel Morgensztern et al.   CANCER

Clinical epigenetics: seizing opportunities for translation

(2018) María Berdasco et al.   NATURE REVIEWS GENETICS

Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors

(2018) Sadegh Saghafinia et al.   Cell Reports

The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells

(2017) Ly P Vu et al.   NATURE MEDICINE

TET-mediated active DNA demethylation: mechanism, function and beyond

(2017) Xiaoji Wu et al.   NATURE REVIEWS GENETICS

Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance

(2017) Sheng Yu Ku et al.   SCIENCE

Novel epigenetic therapies in hematological malignancies: Current status and beyond

(2017) Paolo Gallipoli et al.   SEMINARS IN CANCER BIOLOGY

A comprehensive review of lysine-specific demethylase 1 and its roles in cancer

(2017) Amir Hosseini et al.   Epigenomics

A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma

(2017) Priscila H. Goncalves et al.   Oncotarget

BET Bromodomain Inhibition Synergizes with PARP Inhibitor in Epithelial Ovarian Cancer

(2017) Sergey Karakashev et al.   Cell Reports

Vorinostat in combination with capecitabine plus cisplatin as a first-line chemotherapy for patients with metastatic or unresectable gastric cancer: phase II study and biomarker analysis

(2016) Changhoon Yoo et al.   BRITISH JOURNAL OF CANCER

Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study

(2016) Roisin M. Connolly et al.   CLINICAL CANCER RESEARCH

A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin

(2016) Naris Nilubol et al.   CLINICAL ENDOCRINOLOGY

METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulatingN6-methyladenosine-dependent primary MicroRNA processing

(2016) Jin-zhao Ma et al.   HEPATOLOGY

The Bromodomain and Extra-Terminal Domain (BET) Family: Functional Anatomy of BET Paralogous Proteins

(2016) Yasushi Taniguchi   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia

(2016) Zizhen Feng et al.   Journal of Hematology & Oncology

BET Bromodomain Inhibitors Enhance Efficacy and Disrupt Resistance to AR Antagonists in the Treatment of Prostate Cancer

(2016) I. A. Asangani et al.   MOLECULAR CANCER RESEARCH

Targeting the cancer epigenome for therapy

(2016) Peter A. Jones et al.   NATURE REVIEWS GENETICS

TCPs: privileged scaffolds for identifying potent LSD1 inhibitors for cancer therapy

(2016) Yi-Chao Zheng et al.   Epigenomics

Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin

(2016) Michael J. Overman et al.   Oncotarget

A phase I trial of panobinostat (LBH589) in patients with metastatic melanoma

(2016) Nageatte Ibrahim et al.   Cancer Medicine

Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group

(2015) Michael Lübbert et al.   ANNALS OF HEMATOLOGY

A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC

(2015) Helai P. Mohammad et al.   CANCER CELL

DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts

(2015) David Roulois et al.   CELL

Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses

(2015) Katherine B. Chiappinelli et al.   CELL

Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study

(2015) Owen A. O'Connor et al.   JOURNAL OF CLINICAL ONCOLOGY

Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial

(2015) Lee M Krug et al.   LANCET ONCOLOGY

Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study

(2015) Jean-Pierre J Issa et al.   LANCET ONCOLOGY

N6-methyladenosine marks primary microRNAs for processing

(2015) Claudio R. Alarcón et al.   NATURE

SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2

(2015) Kimberly H Kim et al.   NATURE MEDICINE

Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma

(2015) E. Q. Lee et al.   NEURO-ONCOLOGY

Targeting histone lysine methylation in cancer

(2015) John McGrath et al.   PHARMACOLOGY & THERAPEUTICS

Carboplatin with Decitabine Therapy, in Recurrent Platinum Resistant Ovarian Cancer, Alters Circulating miRNAs Concentrations: A Pilot Study

(2015) Eric A. Benson et al.   PLoS One

DOT1L: a new therapeutic target for aggressive breast cancer

(2015) Jeong-Yeon Lee et al.   Oncotarget

Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery

(2015) Celeste B. Greer et al.   Cell Reports

N6-Adenosine Methylation in MiRNAs

(2015) Tea Berulava et al.   PLoS One

Resistance to everolimus driven by epigenetic regulation of MYC in ER+ breast cancers

(2015) Teeru Bihani et al.   Oncotarget

Decitabine reactivated pathways in platinum resistant ovarian cancer

(2015) Fang Fang et al.   Oncotarget

Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†

(2014) M. Piccart et al.   ANNALS OF ONCOLOGY

An epigenomic approach to therapy for tamoxifen-resistant breast cancer

(2014) Qin Feng et al.   CELL RESEARCH

Structures of Human ALKBH5 Demethylase Reveal a Unique Binding Mode for Specific Single-strandedN6-Methyladenosine RNA Demethylation

(2014) Chao Xu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial

(2014) Jesús F San-Miguel et al.   LANCET ONCOLOGY

Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders

(2014) Katrina J. Falkenberg et al.   NATURE REVIEWS DRUG DISCOVERY

BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones

(2014) Tomohiko Kanno et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

A rationale to target the SWI/SNF complex for cancer therapy

(2014) Anja F. Hohmann et al.   TRENDS IN GENETICS

Lysine-specific histone demethylase LSD1 and the dynamic control of chromatin

(2013) Thomas Rudolph et al.   BIOLOGICAL CHEMISTRY

Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML

(2013) A. Chaturvedi et al.   BLOOD

LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer

(2013) J Ding et al.   BRITISH JOURNAL OF CANCER

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

(2013) Jakob Lovén et al.   CELL

Effects of treatment with histone deacetylase inhibitors in solid tumors: a review based on 30 clinical trials

(2013) Tianzhu Qiu et al.   Future Oncology

Unique functional roles for class I and class II histone deacetylases in central nervous system development and function

(2013) Michael J. Morris et al.   INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE

Randomized Phase II, Double-Blind, Placebo-Controlled Study of Exemestane With or Without Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic Estrogen Receptor-Positive Breast Cancer Progressing on Treatment With a Nonsteroidal Aromatase Inhibitor

(2013) Denise A. Yardley et al.   JOURNAL OF CLINICAL ONCOLOGY

Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia

(2013) M A Dawson et al.   LEUKEMIA

Transcriptional regulation by Polycomb group proteins

(2013) Luciano Di Croce et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

(R)-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible

(2013) J.-A. Losman et al.   SCIENCE

Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation

(2013) F. Wang et al.   SCIENCE

Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: a phase I/II study and pharmacokinetic analysis

(2012) H. A. Tawbi et al.   ANNALS OF ONCOLOGY

Histone Lysine Methylation Dynamics: Establishment, Regulation, and Biological Impact

(2012) Joshua C. Black et al.   MOLECULAR CELL

ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility

(2012) Guanqun Zheng et al.   MOLECULAR CELL

Histone deacetylases and cancer

(2012) Bruna Barneda-Zahonero et al.   Molecular Oncology

IDH mutation impairs histone demethylation and results in a block to cell differentiation

(2012) Chao Lu et al.   NATURE

IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype

(2012) Sevin Turcan et al.   NATURE

EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations

(2012) Michael T. McCabe et al.   NATURE

Intrinsic antiviral immunity

(2012) Nan Yan et al.   NATURE IMMUNOLOGY

Epigenetic protein families: a new frontier for drug discovery

(2012) Cheryl H. Arrowsmith et al.   NATURE REVIEWS DRUG DISCOVERY

Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer

(2012) Tangfeng Lv et al.   PLoS One

EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells Is Polycomb-Independent

(2012) K. Xu et al.   SCIENCE

Epigenetic mechanisms in gastric cancer

(2012) Carolina Oliveira Gigek et al.   Epigenomics

Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma

(2011) R. L. Piekarz et al.   BLOOD

Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation

(2011) S. Y. Jo et al.   BLOOD

MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L

(2011) Kathrin M. Bernt et al.   CANCER CELL

BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc

(2011) Jake E. Delmore et al.   CELL

Outcome of High-Risk Myelodysplastic Syndrome After Azacitidine Treatment Failure

(2011) Thomas Prébet et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase I study of panobinostat in combination with bevacizumab for recurrent high-grade glioma

(2011) J. Drappatz et al.   JOURNAL OF NEURO-ONCOLOGY

RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia

(2011) Johannes Zuber et al.   NATURE

The Polycomb complex PRC2 and its mark in life

(2011) Raphaël Margueron et al.   NATURE

N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO

(2011) Guifang Jia et al.   Nature Chemical Biology

Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

(2011) José Baselga et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mechanisms of Resistance to Decitabine in the Myelodysplastic Syndrome

(2011) Taichun Qin et al.   PLoS One

Novel Agents and Future Directions for Refractory Breast Cancer

(2011) Harold J. Burstein   SEMINARS IN ONCOLOGY

Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non-Small Cell Lung Cancer

(2011) R. A. Juergens et al.   Cancer Discovery

A phase 1 and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum-resistant, epithelial ovarian cancer

(2010) Fang Fang et al.   CANCER

Leukemic IDH1 and IDH2 Mutations Result in a Hypermethylation Phenotype, Disrupt TET2 Function, and Impair Hematopoietic Differentiation

(2010) Maria E. Figueroa et al.   CANCER CELL

Histone H3 Lysine 79 Methyltransferase Dot1 Is Required for Immortalization by MLL Oncogenes

(2010) M.-J. Chang et al.   CANCER RESEARCH

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations

(2010) Sreenath V. Sharma et al.   CELL

The clinical development of histone deacetylase inhibitors as targeted anticancer drugs

(2010) Paul A Marks   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Vorinostat (NSC# 701852) in Patients with Relapsed Non-small Cell Lung Cancer: A Wisconsin Oncology Network Phase II Study

(2010) Anne M. Traynor et al.   Journal of Thoracic Oncology

Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin

(2010) Ryan D Morin et al.   NATURE GENETICS

A Comparison of Azacitidine and Decitabine Activities in Acute Myeloid Leukemia Cell Lines

(2010) Paul W. Hollenbach et al.   PLoS One

Safety and efficacy of azacitidine in myelodysplastic syndromes

(2010) Carlos Vigil et al.   Drug Design Development and Therapy

Histone deacetylase inhibitors as anti-neoplastic agents

(2009) Nicolas Batty et al.   CANCER LETTERS

Lysine-Specific Demethylase 1 Is Strongly Expressed in Poorly Differentiated Neuroblastoma: Implications for Therapy

(2009) J. H. Schulte et al.   CANCER RESEARCH

Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology

(2009) Soyoung Lim et al.   CARCINOGENESIS

Decitabine Effect on Tumor Global DNA Methylation and Other Parameters in a Phase I Trial in Refractory Solid Tumors and Lymphomas

(2009) D. J. Stewart et al.   CLINICAL CANCER RESEARCH

Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma

(2009) Richard L. Piekarz et al.   JOURNAL OF CLINICAL ONCOLOGY

Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study

(2009) Pierre Fenaux et al.   LANCET ONCOLOGY

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

(2009) Lenny Dang et al.   NATURE

Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome

(2009) Elaine R. Mardis et al.   NEW ENGLAND JOURNAL OF MEDICINE

IDH1andIDH2Mutations in Gliomas

(2009) Hai Yan et al.   NEW ENGLAND JOURNAL OF MEDICINE

The Double Bromodomain Proteins Brd2 and Brd3 Couple Histone Acetylation to Transcription

(2008) Gary LeRoy et al.   MOLECULAR CELL

Mammalian DNA Methyltransferases: A Structural Perspective

(2008) Xiaodong Cheng et al.   STRUCTURE