Radiotherapy is an important loco-regional component of modern multimodal cancer therapy. Regardless of considerable progress in cancer therapy, radioresistance is a major problem in several tumor entities. Even with optimal conformal treatment techniques that reduce the volume of normal tissue receiving high doses, adverse reactions in co-irradiated healthy tissue limit the dose that can be applied to the tumor. Widening the therapeutic window between tumor cure and normal-tissue toxicity is required for successful treatment of radioresistant tumors. Furthermore, with an increasing number of cancers being cured or treated as a chronic disease, the risk of developing second cancer after radiotherapy becomes an important issue in long-term survivors, especially in children and young patients. Thus, a better understanding of the early processes leading to tumor cure, normal-tissue reaction, and second cancers, is greatly needed.

The classic view of the biological effect of radiotherapy is based on DNA damage and radiation-induced clonogenic inactivation of target cells in tumors and normal tissue. However, it is becoming increasingly clear that radiation effects on intracellular signaling also contribute to tumor control and late reactions in normal tissue. Radiation-induced extracellular signaling, including cytokines and growth factors from tumor, stromal and immune cells can influence the radiosensitivity of the tumor and can themselves be modulated by radiation. Inflammatory cytokines and chemokines in co-irradiated normal tissue can attract immune cells that are essential for healing the damaged tissue but may also lead to excessive inflammatory or fibrogenic reactions. Hence, the reaction of tumors to radiation cannot be viewed in isolation but should include interactions among cells.

This Research Topic aims at reviewing the current knowledge of in vivo and in vitro radiation effects on cell signaling that are critical to the optimal therapeutic outcome. The aim is to improve the understanding of cellular and molecular mechanisms governing the radiation response of tumors and late tissue effects, including fibrosis and second cancers, and identify potential targets for clinical intervention.

We invite Reviews and Original Research articles focused on radiation responses of tumors and mechanisms of late tissue effects mediated by:
1. Growth factors, cytokines, and chemokines
2. The composition of the tumor microenvironment
3. Innate and adaptive immunity
4. Interactions between tumor and stromal cells
5. Inflammation
6. Angiogenesis and vasculogenesis

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Frontiers in Oncology

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