Fast and Binary Assay for Predicting Radiosensitivity Based on the Theory of ATM Nucleo-Shuttling: Development, Validation, and Performance

The Phosphorylated ATM Immunofluorescence Assay: A High-performance Radiosensitivity Assay to Predict Postradiation Therapy Overreactions

“…To our knowledge, our pATMmax predictive assay performed on skin fibroblasts show the highest performance reported so far -pointing ATM nucleoshuttling as a very good predictor for Human iRS (13)(14)(15). This quantitative correlation was found to be independent of tumor location, cell type and of early or late occurrence of the toxicity (9).…”

“…We are aware that the mandatory cellular amplification step after skin sampling requires several weeks that could appear not suitable for clinical use. However, we are now developing a fast ELISA-assay targeting pATM directly from the original skin sample and with still very interesting performances (average AUC of more than 0.8) and a deadline of a few days for editing the results (14).…”

Cancer Radiotherapy: Understanding the Price of Tumor Eradication

“…Novel functional assays of radiation-induced DNA damage recognition and repair efficiency in ex-vivo irradiated primary human fibroblasts and peripheral blood mononuclear cells (PBMC) have been recently developed. The tests are based on post-irradiation formation of nuclear repair foci at the sites of DNA double-strand breaks (DSBs) for two DNA damage markers, phosphorylated ATM kinase ("ATM nucleo-shuttling") (Bodgi and Foray, 2016;Pereira et al, 2018) and histone H2AX (γ-H2AX) (Martin et al, 2013;Lobachevsky et al, 2015aLobachevsky et al, , 2016. Both assays efficiently separated radiosensitive individuals with impaired DDR from those with normal RS.…”

Modulation of DNA Damage Response by Sphingolipid Signaling: An Interplay that Shapes Cell Fate

“…p-ATM nuclear shuttling and foci formation at DSBs is a very rapid process. The maximal number of nuclear p-ATM foci is usually reached within 10 min to 1 h post-injury [ 50 ]. However, certain cytoplasmic proteins like mutated huntingtin or tuberous sclerosis complex can bind activated ATM monomers and impede their shuttling towards the nucleus [ 49 , 51 ].…”