An anti-inflammatory drug, Ibudilast, has been found to sensitise glioblastoma (GBM) brain tumour cells to Temozolomide, (TMZ), the primary chemotherapy drug, and to increases the efficacy of treatment for recurrent GBM brain tumours.
A new study is recruiting previously treated glioblastoma (GBM) patients to help identify and explain why GBM patients develop a resistance to TMZ (1). Most GBM patients will inevitably experience recurrence after standard treatments of radiotherapy and chemotherapy (writes Gilly Bertram).
GBM is one of the most aggressive forms of brain cancer and stems from the glial cells in the brain. A lot still remains unknown as to the origin of brain tumours and GBM in particular. Some gene expressions such as MGMT (methylguanine-DNA methyltransferase) and IDH-1 (Isocitrate dehydrogenase 1) have been identified to be key components in the formation of glioma brain tumours.
Patients with these mutations appear to have improved prognosis and improved clinical response to treatment. GBM where the patient has MGMT methylation is a target for TMZ. However, despite initial response to TMZ, GBM patients with the MGMT mutation go on to acquire a resistance to TMZ, the reasons for which are not well understood.
Scientists have found another protein that is commonly over-expressed in GBM tumours called macrophage migration factor (MIF). In normal circumstances, MIF is an important regulator of innate immunity, the part of our immune systems which attacks all incoming invaders.
In a study published in Scientific Report (Feb 2019), scientists aimed to see whether the anti-inflammatory drug Ibudilast could show any positive effects since it is known to be a specific MIF inhibitor.
The outcome was that, alone, Ibudilast was unsuccessful but when they combined it with TMZ, they witnessed significant synergistic results including significant anti-proliferative activity due to cell cycle arrest and apoptosis. This means that Ibudilast has a way of sensitizing GBM cells to TMZ and together they stop cancer progression and cause cancer cell death.
Clinical trials have found this repurposed drug to have no adverse side effects and to readily cross the blood brain barrier.
Chris Woollams, former Oxford University Biochemist and a founder of CANCERactive said, "TMZ is the drug used on almost everybody with an astrocytoma or a glioblastoma. It received approval in 1986. It works best when there is methylation, which occurs in just 20% of patients. Even then, GBM builds resistence to it quickly. It is staggering that orthodox medicine has come up with no other answers in all this time. However, there are ways of making TMZ work better and for longer, and even on more people. For example, by using metformin or berberine to restrict sugar, a main driver of brain cancer, and further attack cells through the AMPK pathway. We have also been looking at old, repurposed drugs like Ibudilast, Fenbendazole, Chloroquinone and Mebendazole, and outside the box at melatonin and even the contribution of parasites like Borrelia borgdorferi and yeast infections. There's a lot of interesting research if you know where to look."
Go to: Overview on Brain cancer including treatment alternatives
Reference
- https://www.nature.com/articles/s41598-019-39427-4