Literature DB >> 30537514

Resistance to Epigenetic-Targeted Therapy Engenders Tumor Cell Vulnerabilities Associated with Enhancer Remodeling.

Amanda Balboni Iniguez1, Gabriela Alexe2, Emily Jue Wang1, Giovanni Roti3, Sarvagna Patel4, Liying Chen1, Samuel Kitara1, Amy Conway5, Amanda L Robichaud5, Björn Stolte6, Pratiti Bandopadhayay1, Amy Goodale7, Sasha Pantel7, Yenarae Lee7, Dorian M Cheff8, Matthew D Hall8, Rajarshi Guha8, Mindy I Davis8, Marie Menard9, Nicole Nasholm9, William A Weiss9, Jun Qi10, Rameen Beroukhim11, Federica Piccioni7, Cory Johannessen7, Kimberly Stegmaier12.   

Abstract

Drug resistance represents a major challenge to achieving durable responses to cancer therapeutics. Resistance mechanisms to epigenetically targeted drugs remain largely unexplored. We used bromodomain and extra-terminal domain (BET) inhibition in neuroblastoma as a prototype to model resistance to chromatin modulatory therapeutics. Genome-scale, pooled lentiviral open reading frame (ORF) and CRISPR knockout rescue screens nominated the phosphatidylinositol 3-kinase (PI3K) pathway as promoting resistance to BET inhibition. Transcriptomic and chromatin profiling of resistant cells revealed that global enhancer remodeling is associated with upregulation of receptor tyrosine kinases (RTKs), activation of PI3K signaling, and vulnerability to RTK/PI3K inhibition. Large-scale combinatorial screening with BET inhibitors identified PI3K inhibitors among the most synergistic upfront combinations. These studies provide a roadmap to elucidate resistance to epigenetic-targeted therapeutics and inform efficacious combination therapies.
Copyright © 2018 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  BET inhibition; MYCN; PI3K signaling; drug resistance; enhancer remodeling; neuroblastoma

Mesh：

Substances：

Year:  2018        PMID： 30537514      PMCID： PMC6352909          DOI： 10.1016/j.ccell.2018.11.005

Source DB:  PubMed          Journal:  Cancer Cell        ISSN： 1535-6108            Impact factor:   31.743


  68 in total

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Review 2.  Erlotinib in the treatment of non-small cell lung cancer: current status and future developments.

Authors:  Cesare Gridelli; Paolo Maione; Maria Anna Bareschino; Clorinda Schettino; Paola Claudia Sacco; Rita Ambrosio; Valentina Barbato; Marzia Falanga; Antonio Rossi
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3.  The calculation of microbial assays.

Authors:  C I BLISS
Journal:  Bacteriol Rev       Date:  1956-12

4.  Qualimap: evaluating next-generation sequencing alignment data.

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Journal:  Bioinformatics       Date:  2012-08-22       Impact factor: 6.937

5.  Targeting MYCN in neuroblastoma by BET bromodomain inhibition.

Authors:  Alexandre Puissant; Stacey M Frumm; Gabriela Alexe; Christopher F Bassil; Jun Qi; Yvan H Chanthery; Erin A Nekritz; Rhamy Zeid; William Clay Gustafson; Patricia Greninger; Matthew J Garnett; Ultan McDermott; Cyril H Benes; Andrew L Kung; William A Weiss; James E Bradner; Kimberly Stegmaier
Journal:  Cancer Discov       Date:  2013-02-21       Impact factor: 39.397

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Journal:  Proc Natl Acad Sci U S A       Date:  2014-01-27       Impact factor: 11.205

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Journal:  Nat Genet       Date:  2017-07-24       Impact factor: 38.330

8.  Impact of artifact removal on ChIP quality metrics in ChIP-seq and ChIP-exo data.

Authors:  Thomas S Carroll; Ziwei Liang; Rafik Salama; Rory Stark; Ines de Santiago
Journal:  Front Genet       Date:  2014-04-10       Impact factor: 4.599

9.  Mutational heterogeneity in cancer and the search for new cancer-associated genes.

Authors:  Michael S Lawrence; Petar Stojanov; Paz Polak; Gregory V Kryukov; Kristian Cibulskis; Andrey Sivachenko; Scott L Carter; Chip Stewart; Craig H Mermel; Steven A Roberts; Adam Kiezun; Peter S Hammerman; Aaron McKenna; Yotam Drier; Lihua Zou; Alex H Ramos; Trevor J Pugh; Nicolas Stransky; Elena Helman; Jaegil Kim; Carrie Sougnez; Lauren Ambrogio; Elizabeth Nickerson; Erica Shefler; Maria L Cortés; Daniel Auclair; Gordon Saksena; Douglas Voet; Michael Noble; Daniel DiCara; Pei Lin; Lee Lichtenstein; David I Heiman; Timothy Fennell; Marcin Imielinski; Bryan Hernandez; Eran Hodis; Sylvan Baca; Austin M Dulak; Jens Lohr; Dan-Avi Landau; Catherine J Wu; Jorge Melendez-Zajgla; Alfredo Hidalgo-Miranda; Amnon Koren; Steven A McCarroll; Jaume Mora; Brian Crompton; Robert Onofrio; Melissa Parkin; Wendy Winckler; Kristin Ardlie; Stacey B Gabriel; Charles W M Roberts; Jaclyn A Biegel; Kimberly Stegmaier; Adam J Bass; Levi A Garraway; Matthew Meyerson; Todd R Golub; Dmitry A Gordenin; Shamil Sunyaev; Eric S Lander; Gad Getz
Journal:  Nature       Date:  2013-06-16       Impact factor: 49.962

10.  Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer.

Authors:  Shaokun Shu; Charles Y Lin; Housheng Hansen He; Robert M Witwicki; Doris P Tabassum; Justin M Roberts; Michalina Janiszewska; Sung Jin Huh; Yi Liang; Jeremy Ryan; Ernest Doherty; Hisham Mohammed; Hao Guo; Daniel G Stover; Muhammad B Ekram; Jonathan Brown; Clive D'Santos; Ian E Krop; Deborah Dillon; Michael McKeown; Christopher Ott; Jun Qi; Min Ni; Prakash K Rao; Melissa Duarte; Shwu-Yuan Wu; Cheng-Ming Chiang; Lars Anders; Richard A Young; Eric Winer; Antony Letai; William T Barry; Jason S Carroll; Henry Long; Myles Brown; X Shirley Liu; Clifford A Meyer; James E Bradner; Kornelia Polyak
Journal:  Nature       Date:  2016-01-06       Impact factor: 49.962
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  19 in total

1.  Epigenetic heterogeneity promotes acquired resistance to BET bromodomain inhibition in ovarian cancer.

Authors:  Yunheng Sun; Zhenfeng Zhang; Ke Zhang; Yuxia Liu; Peiye Shen; Meichun Cai; Chenqiang Jia; Wenjing Wang; Zhuowei Gu; Pengfei Ma; Huaiwu Lu; Lei Guan; Wen Di; Guanglei Zhuang; Xia Yin
Journal:  Am J Cancer Res       Date:  2021-06-15       Impact factor: 6.166

Review 2.  Intratumoral Heterogeneity: More Than Just Mutations.

Authors:  Kunihiko Hinohara; Kornelia Polyak
Journal:  Trends Cell Biol       Date:  2019-04-12       Impact factor: 20.808

3.  Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1.

Authors:  Nathaniel W Mabe; Min Huang; Guillermo N Dalton; Gabriela Alexe; Daniel A Schaefer; Anna C Geraghty; Amanda L Robichaud; Amy S Conway; Delan Khalid; Marius M Mader; Julia A Belk; Kenneth N Ross; Michal Sheffer; Miles H Linde; Nghi Ly; Winnie Yao; Maria Caterina Rotiroti; Benjamin A H Smith; Marius Wernig; Carolyn R Bertozzi; Michelle Monje; Constantine S Mitsiades; Ravindra Majeti; Ansuman T Satpathy; Kimberly Stegmaier; Robbie G Majzner
Journal:  Nat Cancer       Date:  2022-07-11

4.  BRD4 Targets the KEAP1-Nrf2-G6PD Axis and Suppresses Redox Metabolism in Small Cell Lung Cancer.

Authors:  Yang Lv; Xiaotong Lv; Jiahui Zhang; Guozhen Cao; Changzhi Xu; Buchang Zhang; Wenchu Lin
Journal:  Antioxidants (Basel)       Date:  2022-03-29

5.  IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia.

Authors:  Brandon J Aubrey; Jevon A Cutler; Wallace Bourgeois; Katherine A Donovan; Shengqing Gu; Charlie Hatton; Sarah Perlee; Florian Perner; Homa Rahnamoun; Alexandra C P Theall; Jill A Henrich; Qian Zhu; Radosław P Nowak; Young Joon Kim; Salma Parvin; Anjali Cremer; Sarah Naomi Olsen; Nicholas A Eleuteri; Yana Pikman; Gerard M McGeehan; Kimberly Stegmaier; Anthony Letai; Eric S Fischer; X Shirley Liu; Scott A Armstrong
Journal:  Nat Cancer       Date:  2022-05-09

6.  Mechanistic basis and efficacy of targeting the β-catenin-TCF7L2-JMJD6-c-Myc axis to overcome resistance to BET inhibitors.

Authors:  Dyana T Saenz; Warren Fiskus; Christopher P Mill; Dimuthu Perera; Taghi Manshouri; Bernardo H Lara; Vrajesh Karkhanis; Sunil Sharma; Stephen K Horrigan; Prithviraj Bose; Tapan M Kadia; Lucia Masarova; Courtney D DiNardo; Gautam Borthakur; Joseph D Khoury; Koichi Takahashi; Srividya Bhaskara; Charles Y Lin; Michael R Green; Cristian Coarfa; Craig M Crews; Srdan Verstovsek; Kapil N Bhalla
Journal:  Blood       Date:  2020-04-09       Impact factor: 22.113

Review 7.  Combining epigenetic drugs with other therapies for solid tumours - past lessons and future promise.

Authors:  Daphné Morel; Daniel Jeffery; Geneviève Almouzni; Sophie Postel-Vinay; Sandrine Aspeslagh
Journal:  Nat Rev Clin Oncol       Date:  2019-09-30       Impact factor: 66.675

Review 8.  Enhancer rewiring in tumors: an opportunity for therapeutic intervention.

Authors:  Laia Richart; François-Clément Bidard; Raphaël Margueron
Journal:  Oncogene       Date:  2021-05-01       Impact factor: 9.867

9.  Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia.

Authors:  Charles C Bell; Katie A Fennell; Yih-Chih Chan; Florian Rambow; Miriam M Yeung; Dane Vassiliadis; Luis Lara; Paul Yeh; Luciano G Martelotto; Aljosja Rogiers; Brandon E Kremer; Olena Barbash; Helai P Mohammad; Timothy M Johanson; Marian L Burr; Arindam Dhar; Natalie Karpinich; Luyi Tian; Dean S Tyler; Laura MacPherson; Junwei Shi; Nathan Pinnawala; Chun Yew Fong; Anthony T Papenfuss; Sean M Grimmond; Sarah-Jane Dawson; Rhys S Allan; Ryan G Kruger; Christopher R Vakoc; David L Goode; Shalin H Naik; Omer Gilan; Enid Y N Lam; Jean-Christophe Marine; Rab K Prinjha; Mark A Dawson
Journal:  Nat Commun       Date:  2019-06-20       Impact factor: 17.694

10.  Concurrent targeting of MAP3K3 and BRD4 by miR-3140-3p overcomes acquired resistance to BET inhibitors in neuroblastoma cells.

Authors:  Chang Liu; Yasuyuki Gen; Kousuke Tanimoto; Tomoki Muramatsu; Jun Inoue; Johji Inazawa
Journal:  Mol Ther Nucleic Acids       Date:  2021-05-11       Impact factor: 8.886
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