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It emphasizes tumor heterogeneity, aggressiveness, limited funding, and preclinical modeling barriers, then describes advances from improved genomic insight and targeted approaches to genetically modified animal models. The issue’s Reviews address key vulnerabilities, molecular and functional heterogeneity, and the tumor microenvironment’s role.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/understanding-brain-cancer-and-exploiting-its-vulnerabilities/331604/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/understanding-brain-cancer-and-exploiting-its-vulnerabilities/331604.png","ImageObject",300,407,{"name":92,"@type":93},"Clementine","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why has brain cancer research historically progressed slowly?","Question",{"text":112,"@type":113},"The text attributes slow progress to dismal prognosis, limited funding, and uncoordinated efforts, along with challenges in preclinical modeling and therapy development.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What recent advances are emphasized as enabling better translation to the clinic?",{"text":117,"@type":113},"Technological advances supporting cancer genome study and drug development or repurposing, plus improved insights into genomic drivers and enhanced preclinical genetically modified animal models.",{"name":119,"@type":110,"acceptedAnswer":120},"How does tumor heterogeneity affect treatment and understanding?",{"text":121,"@type":113},"Heterogeneity includes genetic and epigenetic diversity, underlying aggressiveness, refractoriness to therapy, and rapid progression, and it complicates modeling by failing to fully replicate inter- and intratumor heterogeneity and tumor microenvironment interactions.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331604,1790117380,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},1374391974564,"https://ap-avatar.wpscdn.com/avatar/14000253aa45c000a9e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779874745381141002","EDITORIAL  \nUnderstanding brain cancer and exploiting its vulnerabilities  \nPaolo Salomoni   \nNuclear Function Group, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany  \nCorrespondence  \nP. Salomoni, Nuclear Function Group, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany  \nE-mail: [paolo.salomoni@dzne.de](paolo.salomoni@dzne.de)  \n(Received 31 October 2024, accepted 1 November 2024, available online 25  \nNovember 2024)  \ndoi:10 . 1002/1878-0261 .13769  \nBrain cancer is one of the most devastating neoplasms affecting both children and adults. Its dismal prognosis has for long-time discouraged research in this area. However, in the last 10–15 years remarkable progress has been made in our understanding of brain cancer biology, thus showing promise for the identification of new ways to treat these tumors towards the improvement of patients’ survival and quality of life. This Thematic Issue on Brain cancers offers a much needed and timely critical overview of the fundamental discoveries in this area of research and which of those are more promising for effective translation into the clinic. Critically, many Reviews from this Issue also provide discussion points on why the field has not progressed as much as it had hoped to. It is important to emphasize however that we are living in exciting times with regards to our ability to translate fundamental findings into the clinic thanks to the enormous technological advances facilitating the study of cancer genomes and the development of new drugs or repurposing existing agents.  \nBrain cancers are a group of heterogeneous tumor entities affecting children to adults, representing one of the main causes of death in the working-age population. This is due to their intrinsic aggressiveness and heterogeneity, underlying their refractoriness to therapy and rapid progression even after tumor debulking and aggressive chemo/radiotherapy. Research in this area has been hampered for many years by limited funding and uncoordinated research efforts. However, thanks to enhanced advocacy/awareness and progressively increasing funding, we are gaining key insights into how these tumors develop, which are the main drivers and what role the tumor microenvironment (TME) plays. Our ability to  \nidentify genomic changes driving these neoplasms show promise for developing targeted approaches as part of personalized medicine efforts. Another area of poor progress was preclinical modeling, which in turn hampered progress in our understanding of tumor biology. However, substantial advances have been made in this area with regards to the generation of genetically modified animal models recapitulating the main histological and molecular features of these tumors.  \nThis collection of Reviews aims at covering the main advances and challenges in this area, from preclinical modeling to identification of novel and targetable tumor vulnerabilities.  \nAbbreviations  \n2-HG, 2-hydroxyglutarate; ANG2, Angiopoietin 2; BCR-ABL, breakpoint cluster region-Abelson; c-MET, mesenchymal epithelial transition; CML, chronic myelogenous leukemia; CXCL12, CXC ligand 12; CXCR4, C-X-C Motif Chemokine Receptor 4; EGFR, epidermal growth factor receptor; GBM, glioblastoma multiforme; IDH, isocitrate dehydrogenase enzyme; LDLR, low-density lipoprotein receptor; LGNTs, low-grade neuroepithelial tumors; LRP-1, LDLR-related protein-1; MAPK, mitogen-activated protein kinase; MHC-II, major histocompatibility complex-II; MMR, mismatch repair; NGS, Next generation sequencing; PMMRDIA, primary mismatch repair deficient-IDH-mutated astrocytomas; PTMs, posttranslational modifications; TAM, tumor-associated macrophage; TME, tumor microenvironment; TMs, tumor microtubes.  \nMolecular Oncology 18 (2024) 2817–2821 ª 2024 The Author(s) . Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.  \nThis is an open access article under the terms of ","cbCainXK3hY1VAnh","https://ap.wps.com/l/cbCainXK3hY1VAnh","pdf",132583,"English","# Editorial Overview\n## Advances in preclinical modeling\n## Molecular and functional heterogeneity\n## Abbreviations","[{\"question\":\"Why has brain cancer research historically progressed slowly?\",\"answer\":\"The text attributes slow progress to dismal prognosis, limited funding, and uncoordinated efforts, along with challenges in preclinical modeling and therapy development.\"},{\"question\":\"What recent advances are emphasized as enabling better translation to the clinic?\",\"answer\":\"Technological advances supporting cancer genome study and drug development or repurposing, plus improved insights into genomic drivers and enhanced preclinical genetically modified animal models.\"},{\"question\":\"How does tumor heterogeneity affect treatment and understanding?\",\"answer\":\"Heterogeneity includes genetic and epigenetic diversity, underlying aggressiveness, refractoriness to therapy, and rapid progression, and it complicates modeling by failing to fully replicate inter- and intratumor heterogeneity and tumor microenvironment interactions.\"}]","Understanding brain cancer and exploiting its vulnerabilities | PDF",1789994266,13]