Page 27 - SDIR5 Abstract book 21 12 2021.

RADIOBIOLOGY

Cellular senescence in ionizing radiation

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Bojana Ilic
1 Department of Endocrine Tumors, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical
Center of Serbia, Serbia

Radiotherapy alone or in combination with surgery or chemotherapy is a treatment of choice for many
malignancies, but its efficacy is limited by the dose that can be safely administered as well as the high
incidence of tumor radioresistance, recurrence and metastasis. Ionizing radiation acts by causing DNA
damage that triggers a complex response in tumor and non-tumor cells and tissues. Senescence induced
by ionizing radiation has been considered as a tumor-suppressive mechanism that prevents the
proliferation of genetically unstable and damaged cells. However, an increasing number of studies have
shown that chronic accumulation of senescent cells can, paradoxically, promote cellular transformation,
tumor regrowth and metastasis. Furthermore, there is evidence that suggests that tumor cells can escape
senescence and recover proliferative capacity. These antitumorigenic and protumorigenic effects are
mediated through acquired senescence-associated secretory phenotype (SASP) and undoubtedly depend
on cellular and tissue context. Senescent cells induced by radiation may alter neighbouring
microenvironment via autocrine and paracrine signaling and contribute to additional health problems, such
as fibrosis and cardiovascular disease. Progress in the understanding of the molecular pathways that
regulate senescence in cancer can lead to the discovery of molecular biomarkers and targets for anticancer
therapy. Senotherapeutic agents, including senomorphics (small molecules that are able to modulate
senescent cells activity by reducing or inhibiting SASP generation) and senolytics (agents that induce
apoptosis of senescent cells) have the potential to enhance the efficacy of radiotherapy and/or reduce its
side-effects. The clinical application of senotherapeutics as adjuvants in cancer therapy needs further
investigation.
Keywords: Radiotherapy; Senescence; Senescence Associated Secretory Phenotype;

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