Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery

Abstract

Pediatric brain tumors represent a formidable challenge in the field of oncology. Pediatric brain tumors are sub-classified into several molecular sub-types, where each one is characterized by an array of hyperactivated oncogenic molecular engines. However, there have been great efforts dedicated to portray the involved signaling pathways driving pediatric brain tumors. Yet, a full understanding of the intertwined oncogenic pathways involved is still obscure. In this review, the authors shed light on novel therapeutic targets tailored for several sub-types of pediatric brain tumors and point out the limitations of such therapeutic approaches. Hydrogen Sulfide (H2S) has recently been cast as an oncogenic driver in several solid malignancies, yet its role in brain tumors is still under investigation. The authors also highlight the possible involvement of H2S in pediatric brain tumors and propose promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumors patients.Abstract: 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–brain 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.

Newly Synthesized Anticancer Purine Derivatives Inhibiting p-EIF4E Using Surface-Modified Lipid Nanovesicles

“…Current chemotherapeutics delivery approaches include various nanocarriers, including metallic nanoparticles, polymeric nanoparticles, − macromolecules, , silica nanoparticles, and nanovesicles. , Nanovesicles (liposomes and niosomes) are lipid-based nanocarriers that are reported to encapsulate natural and synthetic chemotherapeutics, enhancing their hydrophilicity and therapeutic effects . Liposomes are formed mainly of phospholipids (such as phosphatidylcholine and phosphatidylethanolamine) self-assembled in an aqueous medium, developing lipid bilayer nanovesicles .…”

Oral Delivery of Psoralidin by Mucoadhesive Surface-Modified Bilosomes Showed Boosted Apoptotic and Necrotic Effects against Breast and Lung Cancer Cells

“…Thus, efforts should be exerted to nanoformulate Ps into a suitable nanosystem which would address the drawbacks hindering its clinical applications. Several nanocarriers are involved in the nanoformulation of different phytochemicals to overcome their limitations and improve their antitumor activities, including vesicular nanocarriers [ 19 , 20 ], polymeric nanoparticles [ 21 , 22 ], supramolecules [ 23 , 24 ], stimuli-responsive delivery systems [ 25 ], and mesoporous silica nanoparticles [ 26 ]. Vesicular nanocarriers, such as liposomes, niosomes, ethosomes, and bilosomes, are promising lipid-based nanosystems for improving hydrophobic drugs’ therapeutic activities [ 27 ].…”

Decoding hepatocarcinogenesis from a noncoding RNAs perspective

“…Many of the genes that include ncRNAs are evolutionarily conserved, much like protein‐coding genes, and have been connected to a variety of biological processes that impact development, differentiation, and several aspects of cellular physiology (Youness & Gad, 2019). It is becoming obvious that abnormal ncRNAs expression is frequently seen in several cancers (Abdallah et al, 2022; Awad et al, 2021; El Din et al, 2021; El Kilany et al, 2021; Fahmy, Dawoud, et al, 2022; Mekky et al, 2023; Nafea et al, 2020; Ramzy et al, 2022; Shaalan et al, 2018; Youness, Rahmoon, et al, 2016; Youness et al, 2018, 2019, 2021, 2022; ZeinElAbdeen et al, 2022), indicating that ncRNAs are important participants in human carcinogenesis (Abdel‐Latif et al, 2022; Ahmed Youness et al, 2020; ElKhouly et al, 2020; Fahmy, Dawoud, et al, 2022; Mekky et al, 2019; Nafea et al, 2021; Soliman et al, 2022; Youssef et al, 2022; ZeinElAbdeen et al, 2022). Recent evidence suggests that these evolutionarily conserved ncRNAs, notably long noncoding RNAs (lncRNAs), PIWI‐interacting RNAs (piRNAs), and circular RNAs (circRNAs), play a significant role in a variety of physiological and pathological processes (Dawoud et al, 2023; Selem et al, 2021).…”

“…LncRNAs play a significant role in HCC initiation, development, progression, and metastasis. Mechanistically, this occurs through its potent capacity in influencing the coding genes expression pattern at multiple levels (Abdallah et al, 2022; Abdel‐Latif et al, 2022; Fahmy, Dawoud, et al, 2022; Nafea et al, 2021). Moreover, the deregulated lncRNAs expression levels between human HCC samples and nontumoral tissues are all noteworthy (El‐Sheikh et al, 2022; Tsang et al, 2015).…”