Proton pump inhibitors and sensitization of cancer cells to radiation therapy

Abstract

This review article outlines six molecular pathways that confer resistance of cancer cells to ionizing radiation, and describes how proton pump inhibitors (PPIs) may be used to overcome radioresistance induced by alteration of one or more of these signaling pathways. The inflammatory, adaptive, hypoxia, DNA damage repair, cell adhesion, and developmental pathways have all been linked to the resistance of cancer cells to ionizing radiation. Here we describe the molecular link between alteration of these pathways in cancer cells and development of resistance to ionizing radiation, and discuss emerging data on the use of PPIs to favorably modify one or more components of these pathways to sensitize cancer cells to ionizing radiation. Understanding the relationship between altered signaling pathways, radioresistance, and biological activity of PPIs may serve as a basis to repurpose PPIs to restore key biological processes that are involved in cancer progression and to sensitize cancer cells to radiation therapy.

Computational approaches for drug repurposing in oncology: untapped opportunity for high value innovation

“…Examples of drugs that are successfully repurposed for oncologic indications include thalidomide (Contergan), a drug originally developed for the treatment of morning sickness and is now marketed for the treatment of multiple myeloma (marketed under the brand name Thalomid). Recently, we have taken the initiative to reformulate and repurpose the antacid drug Esomeprazole (Nexium) for the treatment of radiation dermatitis ( 23 , 24 ). Currently, this study is in phase II clinical trial for the new indication in patients with head and neck cancer (NCT04865731).…”

The Complex Interaction between Proton Pump Inhibitors and Cancer Treatment

“…However, in the treatment of esophageal squamous cell carcinoma, PPIs may enhance the effect of 5-FU [20]. PPIs can also amplify the effects of radiation therapy by reducing the acidity of tumor cells-a phenomenon known as radio-sensitization-which has shown promise in preclinical studies [21].…”

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

“…To address acidity in TME, several researchers have reported that proton pump inhibitors may slow the growth of hepatoblastoma and oesophageal adenocarcinoma [88][89][90]. Proton pump inhibitors, such as omeprazole, esomeprazole, rabeprazole, pantoprazole, or lansoprazole, signifcantly slow the growth and development of neoplasms in individuals with Barrett's oesophagus [91].…”