NOS2 and cancer: Higher RBE of heavy-ions for cancer development have been attributed to a greater non-targeted effects, including bystander effects [38], where bystander effect represents the transmission of oncogenic signals from a directly hit cell to a nearby cell, and the role of pro-inflammatory mediators such as TGFβ1, iNOS, and COX2 in IR-induced bystander effects is well documented [39, 40].