Epigenetic Targeted Therapy for Diffuse Intrinsic Pontine Glioma

Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, with peak incidence in children of 5–7 years of age. In contrast to most types of human cancer, there has been no significant improvement in treatment outcomes for patients with DIPG. Since DIPG occurs in the...

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Veröffentlicht in:Neurologia medico-chirurgica 2017, Vol.57(7), pp.331-342
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description Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, with peak incidence in children of 5–7 years of age. In contrast to most types of human cancer, there has been no significant improvement in treatment outcomes for patients with DIPG. Since DIPG occurs in the brainstem, a vital region of the brain, there are no surgical options for providing relief to patients, and chemotherapy as well as radiation therapy provide palliative relief at best. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy, as well as newer biologic agents, have failed to improve the dismal outcome when compared with palliative radiation alone. The recent discovery of somatic oncogenic histone gene mutations affecting chromatin regulation in DIPG has dramatically improved our understanding of the disease pathogenesis in DIPG, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. This review will discuss about the role of histone modification in chromatin machinery and epigenetic therapeutic strategies for the treatment of DIPG.
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Med. Chir.(Tokyo)</addtitle><description>Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, with peak incidence in children of 5–7 years of age. In contrast to most types of human cancer, there has been no significant improvement in treatment outcomes for patients with DIPG. Since DIPG occurs in the brainstem, a vital region of the brain, there are no surgical options for providing relief to patients, and chemotherapy as well as radiation therapy provide palliative relief at best. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy, as well as newer biologic agents, have failed to improve the dismal outcome when compared with palliative radiation alone. The recent discovery of somatic oncogenic histone gene mutations affecting chromatin regulation in DIPG has dramatically improved our understanding of the disease pathogenesis in DIPG, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. This review will discuss about the role of histone modification in chromatin machinery and epigenetic therapeutic strategies for the treatment of DIPG.</description><subject>Brain stem</subject><subject>Brain Stem Neoplasms - genetics</subject><subject>Brain Stem Neoplasms - pathology</subject><subject>Brain Stem Neoplasms - therapy</subject><subject>Chemotherapy</subject><subject>Children</subject><subject>Chromatin</subject><subject>Clinical trials</subject><subject>Cytotoxicity</subject><subject>demethylation</subject><subject>DIPG</subject><subject>Epigenetics</subject><subject>Glioma</subject><subject>Glioma - genetics</subject><subject>Glioma - pathology</subject><subject>Glioma - therapy</subject><subject>histone</subject><subject>Humans</subject><subject>methylation</subject><subject>Molecular Targeted Therapy</subject><subject>Mutation</subject><subject>Patients</subject><subject>pediatric brain tumor</subject><subject>Radiation therapy</subject><subject>Review</subject><issn>0470-8105</issn><issn>1349-8029</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1vEzEQxS0EolHpnRNaifOmY3v9sRcEKm2oVAkO4Ww53tnE1cYO9m6l_vd4mzaUy8xh3vzm6Q0hHyksGVXyMuzdMtklA6pqAKrfkAXlTVtrYO1bsoBGQa0piDNykbPfALBGN1yr9-SMadEy1egF-Xp98FsMOHpXrW3a4ohdtd5hsofHqo-p-u77fspY3YYx-ZCL7FcMow9YrQYf9_YDedfbIePFcz8nv2-u11c_6rufq9urb3e1Uw0baylty91GtVZoWVxoK5niknOLXd9BT1FZEFRjSzveai1lL4WUjvMNtKzl_Jx8OXIP02aPncPixw7mkPzepkcTrTf_T4LfmW18MKJgFMgC-PwMSPHPhHk093FKoXg2JUJR0mFKFRUcVS7FnBP2pwsUzBy7KbGbZOcdZebYy8qn185OCy8hF8HqKChT7-wQw1Dy-3fedTTglPCFKRTMrTHAOS2lYayAQDWFdHMk3efRbvF0yqbyvwGfvAll1FxeezwJ3M4mg4H_Bcr6rYc</recordid><startdate>2017</startdate><enddate>2017</enddate><creator>HASHIZUME, Rintaro</creator><general>The Japan Neurosurgical Society</general><general>THE JAPAN NEUROSURGICAL SOCIETY</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>2017</creationdate><title>Epigenetic Targeted Therapy for Diffuse Intrinsic Pontine Glioma</title><author>HASHIZUME, Rintaro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c742t-66a93cb79a5864388a6273633aedfd0f1e7a0518e91d398866f6566c33b092933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Brain stem</topic><topic>Brain Stem Neoplasms - genetics</topic><topic>Brain Stem Neoplasms - pathology</topic><topic>Brain Stem Neoplasms - therapy</topic><topic>Chemotherapy</topic><topic>Children</topic><topic>Chromatin</topic><topic>Clinical trials</topic><topic>Cytotoxicity</topic><topic>demethylation</topic><topic>DIPG</topic><topic>Epigenetics</topic><topic>Glioma</topic><topic>Glioma - genetics</topic><topic>Glioma - pathology</topic><topic>Glioma - therapy</topic><topic>histone</topic><topic>Humans</topic><topic>methylation</topic><topic>Molecular Targeted Therapy</topic><topic>Mutation</topic><topic>Patients</topic><topic>pediatric brain tumor</topic><topic>Radiation therapy</topic><topic>Review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HASHIZUME, Rintaro</creatorcontrib><creatorcontrib>Department of Neurological Surgery</creatorcontrib><creatorcontrib>Department of Biochemistry and Molecular Genetics</creatorcontrib><creatorcontrib>Northwestern University Feinberg School of Medicine</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurologia medico-chirurgica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HASHIZUME, Rintaro</au><aucorp>Department of Neurological Surgery</aucorp><aucorp>Department of Biochemistry and Molecular Genetics</aucorp><aucorp>Northwestern University Feinberg School of Medicine</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic Targeted Therapy for Diffuse Intrinsic Pontine Glioma</atitle><jtitle>Neurologia medico-chirurgica</jtitle><addtitle>Neurol. Med. Chir.(Tokyo)</addtitle><date>2017</date><risdate>2017</risdate><volume>57</volume><issue>7</issue><spage>331</spage><epage>342</epage><pages>331-342</pages><issn>0470-8105</issn><eissn>1349-8029</eissn><abstract>Diffuse intrinsic pontine glioma (DIPG) is a rare but uniformly fatal cancer of the brain, with peak incidence in children of 5–7 years of age. In contrast to most types of human cancer, there has been no significant improvement in treatment outcomes for patients with DIPG. Since DIPG occurs in the brainstem, a vital region of the brain, there are no surgical options for providing relief to patients, and chemotherapy as well as radiation therapy provide palliative relief at best. To date, more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy, as well as newer biologic agents, have failed to improve the dismal outcome when compared with palliative radiation alone. The recent discovery of somatic oncogenic histone gene mutations affecting chromatin regulation in DIPG has dramatically improved our understanding of the disease pathogenesis in DIPG, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. This review will discuss about the role of histone modification in chromatin machinery and epigenetic therapeutic strategies for the treatment of DIPG.</abstract><cop>Japan</cop><pub>The Japan Neurosurgical Society</pub><pmid>28592748</pmid><doi>10.2176/nmc.ra.2017-0018</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Brain stem
Brain Stem Neoplasms - genetics
Brain Stem Neoplasms - pathology
Brain Stem Neoplasms - therapy
Chemotherapy
Children
Chromatin
Clinical trials
Cytotoxicity
demethylation
DIPG
Epigenetics
Glioma
Glioma - genetics
Glioma - pathology
Glioma - therapy
histone
Humans
methylation
Molecular Targeted Therapy
Mutation
Patients
pediatric brain tumor
Radiation therapy
Review
title Epigenetic Targeted Therapy for Diffuse Intrinsic Pontine Glioma
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