{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T13:32:59Z","timestamp":1775914379467,"version":"3.50.1"},"reference-count":177,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pediatric primary brain tumors represent a real challenge in the oncology arena. Besides the psychosocial burden, brain tumors are considered one of the most difficult-to-treat malignancies due to their sophisticated cellular and molecular pathophysiology. Notwithstanding the advances in research and the substantial efforts to develop a suitable therapy, a full understanding of the molecular pathways involved in primary brain tumors is still demanded. On the other hand, the physiological nature of the blood\u2013brain barrier (BBB) limits the efficiency of many available treatments, including molecular therapeutic approaches. Hydrogen Sulfide (H2S), as a member of the gasotransmitters family, and its synthesizing machinery have represented promising molecular targets for plentiful cancer types. However, its role in primary brain tumors, generally, and pediatric types, particularly, is barely investigated. In this review, the authors shed the light on the novel role of hydrogen sulfide (H2S) as a prominent player in pediatric brain tumor pathophysiology and its potential as a therapeutic avenue for brain tumors. In addition, the review also focuses on the challenges and opportunities of several molecular targeting approaches and proposes promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumor patients.<\/jats:p>","DOI":"10.3390\/cancers14215244","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T05:11:33Z","timestamp":1666761093000},"page":"5244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-8281","authenticated-orcid":false,"given":"Sherif Ashraf","family":"Fahmy","sequence":"first","affiliation":[{"name":"Chemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Capital City, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyaa","family":"Dawoud","sequence":"additional","affiliation":[{"name":"Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"},{"name":"Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yousra Ahmed","family":"Zeinelabdeen","sequence":"additional","affiliation":[{"name":"Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"},{"name":"Faculty of Medical Sciences\/UMCG, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-9286","authenticated-orcid":false,"given":"Caroline Joseph","family":"Kiriacos","sequence":"additional","affiliation":[{"name":"Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerolos Ashraf","family":"Daniel","sequence":"additional","affiliation":[{"name":"Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Eltahtawy","sequence":"additional","affiliation":[{"name":"Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam Mokhtar","family":"Abdelhalim","sequence":"additional","affiliation":[{"name":"Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Braoudaki","sequence":"additional","affiliation":[{"name":"Clinical, Pharmaceutical, and Biological Science Department, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6268-7942","authenticated-orcid":false,"given":"Rana A.","family":"Youness","sequence":"additional","affiliation":[{"name":"Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"},{"name":"Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3322\/caac.21693","article-title":"Brain and other central nervous system tumor statistics, 2021","volume":"71","author":"Miller","year":"2021","journal-title":"CA A Cancer J. 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