Glioblastoma (GBM) is one of the most lethal central nervous systems (CNS) tumours in adults. As supplements to standard of care (SOC), various immunotherapies improve the therapeutic effect in other cancers. Among them, tumour vaccines can serve as complementary monotherapy or boost the clinical efficacy with other immunotherapies, such as immune checkpoint blockade (ICB) and chimeric antigen receptor T cells (CAR-T) therapy. Previous studies in GBM therapeutic vaccines have suggested that few neoantigens could be targeted in GBM due to low mutation burden, and single-peptide therapeutic vaccination had limited efficacy in tumour control as monotherapy. Combining diverse antigens, including neoantigens, tumour-associated antigens (TAAs), and pathogen-derived antigens, and optimizing vaccine design or vaccination strategy may help with clinical efficacy improvement. In this review, we discussed current GBM therapeutic vaccine platforms, evaluated and potential antigenic targets, current challenges, and perspective opportunities for efficacy improvement.

2023-02-01·Current Topics in Medicinal Chemistry

Multilevel Pharmacological Effects of Antipsychotics in Potential Glioblastoma Treatment

Review

作者: Awuah, Wireko Andrew ; Sikora, Vladyslav ; Cheng Ng, Jyi ; Abdul-Rahman, Toufik ; Mehta, Aashna ; Kalmanovich, Jacob ; Huang, Helen ; Isik, Arda ; Lyndin, Mykola ; Kamanousa, Karl ; Alexiou, Athanasios ; Hasan, Mohammad Mehedi ; Yarlagadda, Rohan ; Kundu, Mrinmoy ; Nansubuga, Esther Patience

Abstract:Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mor-tality rate. Despite current treatment options such as surgery, radiotherapy, and the use of te-mozolomide and bevacizumab, it is considered incurable. Various methods, such as drug reposition-ing, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a cate-gory that was created later. These medications have a high affinity for serotonin receptors such as 5-HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsy-chotics in the treatment of GBM, and an outlook for the field's future progression.

2020-05-01·European Journal of Medicinal Chemistry

Discovery of new LXRβ agonists as glioblastoma inhibitors

Article

作者: Xu, Jun ; Ding, Peng ; Zhang, Zizhen ; Jiang, Fuqiang ; Wei, Junkang ; Gu, Qiong ; Chen, Ziyang ; Zhou, Huihao ; Zhang, Shushu ; Li, Yali ; Chen, Hao

Discovery and optimization of selective liver X receptor β (LXRβ) agonists are challenging due to the high homology of LXRα and LXRβ in the ligand-binding domain. There is only one different residue (Val versus Ile) at the ligand-binding pocket of LXRs. With machine learning methods, we identified pan LXR agonists with a novel scaffold (spiro[pyrrolidine-3,3'-oxindole]). Then, we figured out the mechanism of LXR isoform selectivity from co-crystal structures. Based on the mechanism and the new scaffold, LXRβ selective agonists were designed and synthesized. This led to the discovery of LXRβ agonists 4-7rr, 4-13 and 4-13rr with IC₅₀ values ranging from 1.78 to 6.36 μM against glioblastoma in vitro. Treatment with 50 mg/kg/day of 4-13 for 15 days significantly reduced tumor growth using an in vivo xenograft glioblastoma model.

100 项与 Glioblastoma(Divide and Conquer) 相关的药物交易

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