The potential of metformin as an antineoplastic in brain tumors: A systematic review

Abstract

Brain tumors are challenging to handle and cause severe mortality and morbidity. The primary therapy for brain tumors, a combination of radiotherapy, chemotherapy (i.e temozolomide), and corticosteroids, is considered inadequate to improve patients' clinical conditions and associated with many adverse effects. There is an urgent need for new compounds or repurposing of existing therapies, which could improve brain tumor patients' prognosis. Metformin, commonly used for type 2 diabetes medication, has been examined for its protective action in cancer, reducing cancer risk and cancer-related mortality. However, its effect on cancer is still in rigorous debate. This study examines recent studies on the effects of metformin in primary brain tumor patients through systematic reviews. The literature search was performed on PubMed, ScienceDirect, and SpringerLink databases for articles published between 2013 and 2020. We selected clinical studies comparing the therapeutic outcomes of brain tumor therapy with and without metformin. The clinical benefits of the drug were assessed through the overall survival (OS) and progression-free survival (PFS) of brain tumor patients. Those studies demonstrated that the combination of metformin with temozolomide given post-radiotherapy resulted in better OS and PFS . Nonetheless, the efficacy and safety of metformin need further clinical testing in the wider population.

A Root in Synapsis and the Other One in the Gut Microbiome-Brain Axis: Are the Two Poles of Ketogenic Diet Enough to Challenge Glioblastoma?

“…Interestingly, the gene signature typically induced by the hypoxic GBM microenvironment was partially modified by metformin in a cell model (49). A recent systematic review showed that the combination of metformin with temozolomide given post-radiotherapy achieved better OS and PFS as compares with temozolomide alone (50). However, a recent pooled analysis produced opposite results (26).…”

Metformin and Risk of Malignant Brain Tumors in Patients with Type 2 Diabetes Mellitus

“…The mechanisms of the potential protective effect of metformin on MBT remain unknown, but some biological effects of metformin can explain such an observation. MBT cells are dependent on glucose metabolism (a phenomenon known as the Warburg effect) and the mammalian target of rapamycin (mTOR) signaling to support their proliferation and growth [18,30]. Metformin inhibits the mitochondrial complex 1 of electron transport and reduces energy supply to cancer cells [12,18].…”

“…MBT cells are dependent on glucose metabolism (a phenomenon known as the Warburg effect) and the mammalian target of rapamycin (mTOR) signaling to support their proliferation and growth [18,30]. Metformin inhibits the mitochondrial complex 1 of electron transport and reduces energy supply to cancer cells [12,18]. Metformin has been shown to inhibit glioblastoma cell growth and induce cell cycle arrest, autophagy, and apoptosis in in vitro studies.…”

“…After oral intake, metformin can cross the blood-brain barrier and distribute to the brain tissues [16,17]. In recent years, the potential usefulness of metformin on the treatment of MBT has been investigated [18]. According to in vitro and in vivo studies, metformin may inhibit the growth of human glioblastoma cells and enhance therapeutic responses to chemotherapy (e.g., temozolomide) and radiotherapy [18][19][20].…”

“…In recent years, the potential usefulness of metformin on the treatment of MBT has been investigated [18]. According to in vitro and in vivo studies, metformin may inhibit the growth of human glioblastoma cells and enhance therapeutic responses to chemotherapy (e.g., temozolomide) and radiotherapy [18][19][20]. Several clinical trials are being conducted to investigate its potential usefulness in the treatment of MBT but the outcomes remain unknown [17,21,22].…”