Low-Dose Radiation Therapy (LDRT) against Cancer and Inflammatory or Degenerative Diseases: Three Parallel Stories with a Common Molecular Mechanism Involving the Nucleoshuttling of the ATM Protein?

SIMPLE SUMMARY: We reviewed the medical applications of low-dose radiation therapy (LDRT) in cancer and inflammatory and degenerative diseases by proposing a unified mechanistic model based on the radiation-induced nucleoshuttling of the ATM kinase to better understand the interest in low-dose of radiation. ABSTRACT: Very early after their discovery, X-rays were used in multiple medical applications, such as treatments against cancer, inflammation and pain. Because of technological constraints, such applications involved X-ray doses lower than 1 Gy per session. Progressively, notably in oncology, the dose per session increased. However, the approach of delivering less than 1 Gy per session, now called low-dose radiation therapy (LDRT), was preserved and is still applied in very specific cases. More recently, LDRT has also been applied in some trials to protect against lung inflammation after COVID-19 infection or to treat degenerative syndromes such as Alzheimer’s disease. LDRT illustrates well the discontinuity of the dose-response curve and the counterintuitive observation that a low dose may produce a biological effect higher than a certain higher dose. Even if further investigations are needed to document and optimize LDRT, the apparent paradox of some radiobiological effects specific to low dose may be explained by the same mechanistic model based on the radiation-induced nucleoshuttling of the ATM kinase, a protein involved in various stress response pathways.