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Microbes & Immunity Glioblastoma therapy: Immunotherapy and inhibitors

drug must contain conjugated rings of varying saturation Conflict of interest
and aromaticity conducive to permeation across the GBM
tumor microenvironment. An analysis of the American The authors declare that they have no competing interest.
Chemical Society’s recent review on all anti-GBM SMIs Author contributions
in active clinical trials reveals that nitrogen, particularly
the oxygenated trialkylamine nitrogen, is a vital driver of Conceptualization: Matthew A. Abikenari, Daniel M.
active drug candidates with the potential for effective anti- Fountain, Maria Isabel Leite
GBM therapy. 89,97 The prominent role of alkylamines such Writing–original draft: Matthew A. Abikenari, Iman
as morpholine, piperazine, and dimethylamine as oxidative Enayati, Daniel M. Fountain
metabolites partly mediates this response. However, there Writing–review & editing: Matthew A. Abikenari, Iman
is also increasing attention placed on the potential role Enayati, Daniel M. Fountain
of trialkylamines as elevators of the oil-water partition
coefficient of SMIs, leading to enhanced antitumor Ethics approval and consent to participate
activity. 98,99 Therefore, an effective strategy to uncover the Not applicable.
therapeutics of novel SMIs as potential anti-GBM drugs is
to examine the overlapping biochemical structures of pre- Consent for publication
existing SMIs that have yielded pharmacokinetic efficacy Not applicable.
in prior trials. A detailed summary of SMIs in glioblastoma
therapy is shown in Table 3. Availability of data

7. Conclusion Not applicable.
Although GBM remains an incurable condition, the future References
of neuro-oncology appears promising. Over the past
decade, our understanding of angiogenesis, nanomedicine, 1. Omuro A. Glioblastoma and other malignant gliomas:
A clinical review. JAMA. 2013;310(17):1842.
medicinal chemistry, and immunotherapy has already led
to an accumulation of highly effective therapeutic strategies doi: 10.1001/jama.2013.280319
for cancers that were previously deemed incurable. 2. Thakkar JP, Dolecek TA, Horbinski C, et al. Epidemiologic
Undeniably, the GBM tumor microenvironment remains and molecular prognostic review of glioblastoma. Cancer
an immunologically distinct avenue, blocked by the BBB/ Epidemiol Biomarkers Prev. 2014;23(10):1985-1996.
BBTB and further complicated by a highly heterogeneous doi: 10.1158/1055-9965.epi-14-0275
tumor genome. Nevertheless, current literature points
to a promising, new treatment direction, which is 3. Tamimi AF, Juweid M. Epidemiology and outcome of
contingent on the body’s immunogenic responses and glioblastoma. In: Glioblastoma. Brisbane, AU: Codon
the delivery of novel drugs that demonstrate high safety Publications; 2017. p. 143-153.
profile, selective pharmacokinetics and low cytotoxicity. doi: 10.15586/codon.glioblastoma.2017.ch8
In particular, checkpoint inhibitors, immunotherapeutic 4. Ostrom QT, Gittleman H, Fulop J, et al. CBTRUS statistical
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Immunotherapeutic vaccines, ICIs, and SMIs offer highly doi: 10.1093/neuonc/nov189
personalized, precision-based molecular strategies that
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immunotherapies and pharmacologically selective SMIs
that can penetrate and survive the harsh microenvironment doi: 10.1007/s11060-011-0738-7
of GBM tumor cells. 6. Malmström A, Grønberg BH, Marosi C, et al.
Temozolomide versus standard 6-week radiotherapy versus
Acknowledgments hypofractionated radiotherapy in patients older than
None. 60 years with glioblastoma: The nordic randomised, phase 3
trial. Lancet Oncol. 2012;13(9):916-926.
Funding doi: 10.1016/s1470-2045(12)70265-6
None. 7. Zhang H, Wang R, Yu Y, Liu J, Luo T, Fan F. Glioblastoma

Volume 2 Issue 4 (2025) 138 doi: 10.36922/mi.5075