Metformin: (future) best friend of the radiation oncologist?. (October 2020)

• Record Type: Journal Article
• Authors: Chevalier, Benjamin; Pasquier, David; Lartigau, Eric Felix; Chargari, Cyrus; Schernberg, Antoine; Jannin, Arnaud; Mirabel, Xavier; Vantyghem, Marie-Christine; Escande, Alexandre
• Is Part Of: Radiotherapy and oncology. Volume 151(2020)
• Page Start: 95
• Page End: 105
• Publication Date: 2020-10
• Subjects: MTF Metformin -- RT radiation therapy -- RCT chemoradiotherapy -- AMPK AMP-activated protein kinase -- AMP adenosine monophosphate -- OCT1/3 organic cation transporters 1 and 3 -- MATE1/2 multidrug and toxin extrusion proteins 1 and 2 -- m3GPD mitochondrial glycerol-3-phosphate dehydrogenase -- ATP adenosine triphosphate -- mTOR mechanistic target of rapamycin -- ROS reactive oxygen species -- ATM ataxia telangiectasia mutated protein -- CSC cancer stem cells -- HNSCC head and neck squamous cell carcinoma -- FASN fatty acid synthase -- NSCLC non-small cell lung cancer -- PD-L1 programmed death-ligand 1 -- pCR pathologic complete response -- DFS disease free survival -- RFS recurrence free survival -- PFS progression free survival -- MFS metastasis free survival -- OS overall survival; Metformin -- Radiotherapy -- Radiation-sensitizing agents -- AMPK kinase; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2020.06.030
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: Metformin is an antidiabetic drug with potentially radiosensitizing properties. Preclinical data propose numerous mechanisms. Retrospective studies suggest benefits in PFS and OS in multiples localizations. Metformin could also limit RT-induced toxicities on healthy tissue. Several clinical trials are ongoing. Abstract: Several molecules are being investigated for their ability to enhance the anti-tumor effect of radiotherapy. The widely prescribed antidiabetic drug metformin has been suggested to possess anti-cancer activity; data indicate that metformin could also enhance radiation sensitivity. The purpose of this review is to summarize current knowledge on the specific effect of metformin in the field of RT, while also discussing the many unknowns that persist. Preclinical models point to multiple mechanisms involved in the radiosensitizing effects of metformin that are mainly linked to mitochondrial complex I inhibition and AMP-activated protein kinase. Transposition of results from bench to bedside will be discussed through the lens of the drug concentration, its potential limits in human settings, and possible alternatives. Clinical data suggest metformin improves progression-free and overall survival in patients for many different cancers treated with RT; nevertheless, the results are not always consistent. The main limitations of the reviewed literature are the retrospective nature of studies, and most of the time, a lack of information on MTF treatment duration and the administered dosages. Despite these limitations, the possible mechanisms of the role of metformin and its utility in enhancing radiotherapy treatments are analyzed. Ongoing clinical trials are also discussed.