Advances in mitophagy and mitochondrial apoptosis pathway-related drugs in glioblastoma treatment

Abstract

Glioblastoma (GBM) is the most common malignant tumor of the central nervous system (CNS). It is a leading cause of death among patients with intracranial malignant tumors. GBM exhibits intra- and inter-tumor heterogeneity, leading to drug resistance and eventual tumor recurrence. Conventional treatments for GBM include maximum surgical resection of glioma tissue, temozolomide administration, and radiotherapy, but these methods do not effectively halt cancer progression. Therefore, development of novel methods for the treatment of GBM and identification of new therapeutic targets are urgently required. In recent years, studies have shown that drugs related to mitophagy and mitochondrial apoptosis pathways can promote the death of glioblastoma cells by inducing mitochondrial damage, impairing adenosine triphosphate (ATP) synthesis, and depleting large amounts of ATP. Some studies have also shown that modern nano-drug delivery technology targeting mitochondria can achieve better drug release and deeper tissue penetration, suggesting that mitochondria could be a new target for intervention and therapy. The combination of drugs targeting mitochondrial apoptosis and autophagy pathways with nanotechnology is a promising novel approach for treating GBM.This article reviews the current status of drug therapy for GBM, drugs targeting mitophagy and mitochondrial apoptosis pathways, the potential of mitochondria as a new target for GBM treatment, the latest developments pertaining to GBM treatment, and promising directions for future research.

Orexin‐A mediates glioblastoma proliferation inhibition by increasing ferroptosis triggered by unstable iron pools and GPX4 depletion

“…In addition, the combination of drugs targeting both mitochondrial apoptosis and ferroptosis is a promising new approach for GBM treatment. 32 , 33 Orexin‐A shows significant ferroptosis inducing potential in glioma, but whether it can induce apoptosis needs further study. But in any case, as a potential inducer of ferroptosis in GBM, orexin‐A is a promising antitumor drug.…”

A Phyto-mycotherapeutic Supplement, Namely Ganostile, as Effective Adjuvant in Brain Cancer Management: An In Vitro Study Using U251 Human Glioblastoma Cell Line

“…The idea of an activated cell death mechanism is also corroborated by the strong alteration in Golgi observed already after Ganostile treatment, which became more evident in both Ganostile + Cisplatin and Ganostile + Pt(IV)Ac-POA treated cells. Moreover, mitochondria, another key cellular organelle whose dysfunction plays a crucial role in survival, metabolism, proliferation, and cell death of glioblastoma, are found to be deeply compromised after Ganostile + Cisplatin and Ganostile + Pt(IV)Ac-POA treatments, possibly resulting in mitophagy and mitochondrial apoptosis pathways activation [ 25 ]. Parallelly, the activation of cell death pathways is confirmed by the increase in lysosome expression levels, clearly observable after the use of the fourth-generation platinum compound, alone or in combination with our mycotherapeutic blend.…”

Crebanine, an aporphine alkaloid, induces cancer cell apoptosis through PI3K-Akt pathway in glioblastoma multiforme

“…It has been found to activate autophagy and mitophagy via the PI3K pathway. Future research on its clinical applicability is still needed ( Li and Xu, 2023 ). Buparlisib, a BBB-penetrating panPI3K inhibitor, has shown potent inhibitory effects on GBM, both in vitro and in vivo .…”