Fig 1. The effects of IR in normal tissue regeneration and in cancer therapy.

IR is used to treat tumors in human cancers but can also be utilized to model tissue damage and regeneration after injury. (Left) In normal tissues consisting of diverse cell types (depicted as differently colored cells), IR induces cell death, and AIP can stimulate surviving cells to repopulate the damaged tissues. As cells proliferate, cell competition between pools with different proliferative capacities may occur. As a consequence, cells may contribute via different mechanisms to regenerate tissues, including proliferating to replace dead cells, undergoing apoptosis, and translocating and changing identity (gray cells) to fully regenerate all cell types in the tissue. (Right) Similar pathways may be activated after IR treatment of tumors. However, genetic changes (green or pink hexagonal nuclei) in cancer cells abnormally increase proliferative capacity and suppress apoptosis. These properties can lead to oncogene-driven cell competition within the tumor mass after irradiation, leading to expansion of cancer cell pools. Attempts to regenerate the tissue, however, are deregulated as oncogenes can drive overproliferation of tumor cells, evade apoptotic signals, and generate cancer stem-like populations of cells (gray cells with pink hexagons) that can regain proliferative capacity. Ultimately, the newly evolved tumor lacks signals that would restrict growth and normal development and will be genetically and biochemically distinct from the initial IR-treated tumor. AIP, apoptosis-induced proliferation; IR, ionizing radiation.