Medicina Nuclear e Radioterapia

Role of Therapy-Induced Cellular Senescence in Tumor Cells and its Modification in Radiotherapy: The Good, The Bad and The Ugly

Abstract

David Murray and Razmik Mirzayans

The last decade has seen major advances in the clinical practice of radiotherapy (RT). Our understanding of the biological effects occurring after exposure of cells and tissues to ionizing radiation has also increased enormously in this period. In this article we will summarize our current knowledge and key knowledge gaps in an area that is emerging as a potentially important factor in tumor responses to RT, namely the activation of the therapy-induced cellular senescence (TCS) pathway and its associated secretory response, the so-called senescence-associated secretory phenotype or “SASP”. Although the existing literature on these responses is substantial in the chemotherapy domain, the information specific to RT has unfortunately lagged behind. This includes knowledge relating to the factors that govern the ability of tumor cells to switch from TCS to another terminal/irreversible mode of cell death or to escape from TCS and recover proliferative potential. We will therefore examine some of the implications of TCS and SASP from the perspectives of better understanding the biological basis of the various types of RT delivery. We will also consider the implications of this knowledge for the development and use of modifying agents that either reinforce the TCS phenotype and circumvent recovery pathways or switch the cells from TCS into a terminal apoptotic pathway that may represent a more desirable outcome clinically.