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. |
doi_str_mv | 10.2176/nmc.ra.2017-0018 |
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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><identifier>ISSN: 0470-8105</identifier><identifier>EISSN: 1349-8029</identifier><identifier>DOI: 10.2176/nmc.ra.2017-0018</identifier><identifier>PMID: 28592748</identifier><language>eng</language><publisher>Japan: The Japan Neurosurgical Society</publisher><subject>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</subject><ispartof>Neurologia medico-chirurgica, 2017, Vol.57(7), pp.331-342</ispartof><rights>2017 by The Japan Neurosurgical Society</rights><rights>Copyright Japan Science and Technology Agency 2017</rights><rights>2017 The Japan Neurosurgical Society 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c742t-66a93cb79a5864388a6273633aedfd0f1e7a0518e91d398866f6566c33b092933</citedby><cites>FETCH-LOGICAL-c742t-66a93cb79a5864388a6273633aedfd0f1e7a0518e91d398866f6566c33b092933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566706/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566706/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1884,4025,27928,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28592748$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Epigenetic Targeted Therapy for Diffuse Intrinsic Pontine Glioma</title><title>Neurologia medico-chirurgica</title><addtitle>Neurol. 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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