Basic Principles of Radiobiology and Cancer Metastasis Prevention

Basic biological principles of tumor cells and tissue responses to therapeutic ionizing radiation are presented in the context of metastasis prevention. Focuses include a description of cell survival, reassortment (cell cycle position), reoxygenation, repopulation, repair, radiosensitivity, and the influence of the hypoxic tumor microenvironment. We emphasize understanding the confounding factors of the tumor microenvironment and tumor interaction with ever-changing microenvironments during tumor progression, including examples of how the tumor microenvironment influences tumor sensitivity to ionizing radiation. Microenvironments change in response to tumor invasion, and irradiation influences the microenvironment, suggesting that integrated responses to radiation occur between the tumor and the microenvironment. Future research will require increased understanding of both tumor subtypes and the spatial and temporal interactions of the microenvironment as tumors locally invade and metastasize. Prostate cancer acts as an example in which extraprostatic extension of disease into the periprostatic adipose tissue has unknown influences on radiation therapy responses but may account, in part, for the reported limited therapeutic responses in obese patients. Understanding the integrated responses of tumor with the changing microenvironment during the early stages of metastasis holds potential for identifying new targets to improve tumor eradication by ionizing radiation and preventing tumor metastasis or recurrent disease.