Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity

Novel particle therapy was implemented into standard-of-care for cancer patients during the
last years. However, experimental studies investigating cellular and molecular mechanisms
are lacking and prognostic biomarker are urgently needed. Cancer stem cell
(CSC)-related biomarkers such as aldehyde dehydrogenase (ALDH) are known to cellular radiosensitivity by affecting defense against reactive
oxygen species, DNA damage repair and cell survival. Within a previous study, we found that ionizing radiation itself enriches for
ALDH-positive CSCs.
Within the present study, we investigated CSC marker dynamics in prostate cancer, head and neck cancer and glioblastoma cells upon proton beam irradiation. We found that proton irradiation has an increased CSC targeting potential, reduced methylation of activating histone marks and
a lower induction of cellular senescence compared to conventional photon irradiation. Interestingly, mathematical modeling
indicated to differences in plasticity rates among ALDH-positive CSCs and ALDH-negative cancer cells between the two irradiation types.