Abstract
Abstract Survival of pediatric and young adults with malignant glioma remains poor despite progress in treatment. This is especially true for histone 3.3 G34R/V (H3.3G34R/V) mutated gliomas, which often present in adolescent and young adult patients. While treatments to date delay progression, post 5-year overall survival is exceedingly rare. Historically, there has been limited research on H3G34R/V mutant tumors, which likely contributes to lack of advancements in current treatments. This scoping review fills the current knowledge gap of H3G34R/V mutated gliomas and summarizes future targets and therapeutic options. In October 2023, MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection were searched. Two reviewers screened all articles by title and abstract review and three independent reviewers extracted all studies meeting inclusion criteria relevant to H3G34R/V tumors (preclinical and clinical studies). Of the 2203 articles screened, 200 were deemed eligible. The 200 articles included 68 literature reviews, 9 systematic reviews, 54 preclinical studies, and 69 clinically oriented studies. We found that the United States and ACTA neuropathologica are the top country and journal contributors, respectively, to understanding molecular diagnosis, disease pathology, and potential targeted treatment options of H3.3G34R/V tumors. This literature collectively demonstrates the involvement of numerous oncogenes and tumor suppressor genes involved in RAS/MAPK, MYCN, NOTCH, and LIF/STAT pathways such as ATRX, PDGFRA, and TP53 in influencing the neural characteristics and prognostic outcomes of the tumor. While certain therapeutic modalities, including H3K9 methyltransferase inhibitors and bevacizumab-based therapy have exhibited preclinical efficacy and some indication of positive clinical outcomes, more research on agents that permeate the blood-brain barrier to impair growth are necessary. Additionally, further research into the supportive role of the tumor microenvironment that enables disease progression is warranted. Collectively, these studies will empower intelligent prospective clinical trials using H3.3G34R/V targeted therapies which enhance disease survival.
Published Version
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