Abstract
Despite numerous advancements in the last decade, human gliomas such as astrocytoma and glioblastoma multiforme have the worst prognoses among all cancers. Anti-psychotic drugs are commonly prescribed to treat mental disorders among cancer patients, and growing empirical evidence has revealed their antitumor, anti-metastatic, anti-angiogenic, anti-proliferative, chemo-preventive, and neo-adjuvant efficacies in various in vitro, in vivo, and clinical glioma models. Anti-psychotic drugs have drawn the attention of physicians and researchers owing to their beneficial effects in the prevention and treatment of gliomas. This review highlights data on the therapeutic potential of various anti-psychotic drugs as anti-proliferative, chemopreventive, and anti-angiogenic agents in various glioma models via the modulation of upstream and downstream molecular targets involved in apoptosis, autophagy, oxidative stress, inflammation, and the cell cycle in in vitro and in vivo preclinical and clinical stages among glioma patients. The ability of anti-psychotic drugs to modulate various signaling pathways and multidrug resistance-conferring proteins that enhance the efficacy of chemotherapeutic drugs with low side-effects exemplifies their great potential as neo-adjuvants and potential chemotherapeutics in single or multimodal treatment approach. Moreover, anti-psychotic drugs confer the ability to induce glioma into oligodendrocyte-like cells and neuronal-like phenotype cells with reversal of epigenetic alterations through inhibition of histone deacetylase further rationalize their use in glioma treatment. The improved understanding of anti-psychotic drugs as potential chemotherapeutic drugs or as neo-adjuvants will provide better information for their use globally as affordable, well-tolerated, and effective anticancer agents for human glioma.
Highlights
Cancer is prevalent globally, and with growing health apprehension and therapeutic developments, its mortality rate is still alarming [1, 2]
The efficacy of anti-psychotic drugs as anticancer agents or adjuvants in glioma therapy could be attributed to their therapeutic concentrations
Recent reports that studied the effects of anti-psychotic drugs at a lower range of concentrations might suggest lower concentrations may be worthy of investigation
Summary
With growing health apprehension and therapeutic developments, its mortality rate is still alarming [1, 2]. A recent report in 2017 estimated 23,800 new cases of brain and central nervous tumor (CNS) tumors out of 1,688,780 new cases estimated in the United States alone. Despite the low prevalence as compared with other cancers, the statistical rate of mortality from glioma and other related brain tumors is estimated to be around 70% in the year 2017 alone [3]. Glioma, which refers to tumors of glial cell origin, is the most common type of central CNS tumor and constitutes more than 30% of all primary brain and CNS malignant tumors [4]. There is no available cure for GBM despite some therapeutic advancements in the last decade.
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