Simplifying the Biology: Stem, Stroma and Beyond

Hypofractionated radiation therapy (RT) was first used in the early twentieth century. Since then technological improvements have made dose delivery more precise, reducing concern about deleterious effects of large single doses to critical organs. In parallel, a better understanding is required of the biological aspects of large dose radiation effects in both normal and malignant tissue. Tissue responses to radiation are regulated by multiple factors starting from stem progenitor cell populations, the tissue microenvironment including the stromal niche, and major signaling cross-talk between the stem cell compartment, stroma, and the immune microenvironment, not only locally but also systemically via abscopal effects. Recent studies indicated that the gut microbiome also plays a significant role in malignancy, not only its natural history but also its response to therapeutic interventions. This chapter will cover these new biological factors and mechanisms, and their involvement in the overall consequences of hypofractionated RT.