The effects of FLASH RT on normal bronchial epithelial stem cells

ESR Secondment – Lorena Giuranno – Institut Curie (March-April 2018 and August-September 2018)

Radiotherapy (RT) is often limited because of side-effects in normal tissue which negatively affects local tumour control and patient’s quality of life. There is an urgent need to develop new strategies that limit toxicity while keeping the antitumoral efficacy.  Favaudon et al., showed that using FLASH irradiation with high dose-rate (several Gy per ns) decreases the occurrence of fibrosis in irradiated lung and prevents the activation of the TGF-β cascade observed with conventional irradiation. FLASH spared epithelial cells from apoptosis and might reduce the occurrence of early and late complications affecting normal tissue (Favaudon et al., 2014). Though FLASH effect was observed by different teams on animal models, it has never been observed in cell culture.

During this secondment I have visited the laboratory of Recombination, Repair and Cancer of Dr Marie Dutreix at Institute Curie to compare the effects of FLASH (flRT) and conventional irradiation (cRT) of primary human bronchial epithelial cells and lung cancer cells. While flRT and cRT were equally effective in a dose dependent manner to reduce clonogenic survival of lung cancer cells, on normal primary lung bronchial epithelial cells flRT increased the number of S-phase cells compared to cRT. We are now comparing the effects of flRT and cRT on terminal differentiation of lung epithelial stem cells in to differentiated progeny.

Reference: Favaudon, Caplier, Monceau, Pouzoulet, Sayarath, Fouillade, Poupon, Brito, Hupé,
Bourhis, Hall, Fontaine, Vozenin. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci Transl Med. 2014 Jul 16;6(245):245ra93.
doi: 10.1126/scitranslmed.3008973