Proton pump inhibitors display anti‐tumour potential in glioma

Abstract

Objectives: Glioma is one of the most aggressive brain tumours with poor overall survival despite advanced technology in surgical resection, chemotherapy and radiation.Progression and recurrence are the hinge causes of low survival. Our aim is to explain the concrete mechanism in the proliferation and progression of tumours based on tumour microenvironment (TME). The main purpose is to illustrate the mechanism of proton pump inhibitors (PPIs) in affecting acidity, hypoxia, oxidative stress, inflammatory response and autophagy based on the TME to induce apoptosis and enhance the sensitivity of chemoradiotherapy.Findings: TME is the main medium for tumour growth and progression. Acidity, hypoxia, inflammatory response, autophagy, angiogenesis and so on are the main causes of tumour progress. PPIs, as a common clinical drug to inhibit gastric acid secretion, have the advantages of fast onset, long action time and small adverse reactions.Nowadays, several kinds of literature highlight the potential of PPIs in inhibiting tumour progression. However, long-term use of PPIs alone also has obvious side effects. Therefore, till now, how to apply PPIs to promote the effect of radiochemotherapy and find the concrete dose and concentration of combined use are novel challenges.Conclusions: PPIs display the potential in enhancing the sensitivity of chemoradiotherapy to defend against glioma based on TME. In the clinic, it is also necessary to explore specific concentrations and dosages in synthetic applications. | BACKGROUNDGlioma is one of the most aggressive brain tumours. Histologically, the World Health Organization (WHO) classified the tumours of the central nervous system (CNS) into astrocytomas, oligodendrogliomas and ependymoma. In addition, gliomas are classified into four grades according to the degree of malignancy. Types I and II are low-grade gliomas and types III and IV are high-grade gliomas. [1][2][3] The clinical cure rate and 5-year survival rate of patients are all very low. The prognosis is very dismal and the average survival period is only about 1 year. One of the main reasons for the poor prognosis of patients is that glioma is prone to drug resistance to chemoradiation therapy resistance. 4,5 Therefore, it is urgent to explore new strategies for glioma treatment.Pump proton inhibitors (PPIs) are a drug of choice for inhibiting gastric acid secretion. In clinical, they are the first-line option to treat peptic ulcers, gastroesophageal reflux disease, zoai syndrome and upper gastrointestinal bleeding. 6,7 It has become the first-line drug for abnormal gastric acid secretion and related diseases combined with amoxicillin, clarithromycin and other drugs to treat Helicobacter pylori infection. 8,9 PPIs have the advantages of fast onset, strong acid inhibition, long action time, low blood drug concentration and low

Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence

“…PPIs could also have important antitumor effects, as has been reviewed elsewhere [36]. A variety of action mechanisms have been proposed and include the following: immunopotentiation [37], sensitization to chemoradiotherapy [38], the promotion of apoptosis and suppression of migration [39], detoxification inhibition [40], and the suppression of exosomes carrying microRNA [41], among others.…”