Advances in Biological Understanding of Tumor Radiation Resistance

Radiation therapy (RT) is a frequently-applied powerful treatment approach generally leading to enhanced local tumor control. However, a clinical outcome may be compromised by ineffective eradication of cancer cells that exhibit intrinsic or acquired radiation resistance. Although with increased doses of irradiation these radioresistant carcinoma cells can successfully be killed, it is usually impossible to reach these doses without pronounced damage to healthy tissue. To enhance the efficacy of RT, it is important to elucidate the molecular mechanisms regulating radiation resistance of tumor cells. The development of novel chemo- or targeting therapeutics targeting these mechanisms may thereby improve RT efficacy.

A number of intracellular signaling pathways are already known to be involved in cancer cell insensitivity to irradiation. Among them are mutations in genes related to DNA damage and repair, activation of intracellular pro-survival signaling pathways, affected cell cycle regulation, compromised cell death machinery, etc. However, microenvironmental factors may also be foreseen to be involved in tumor cell radioresistance. Thus, hypoxia, tumor-associated fibroblasts, immune system cells, micro- and macrophages could also diminish tumor responses to ionizing radiation. Additionally, cancer stem cells (CSC) encapsulate in a single concept many of the above-mentioned explanations of tumor insensitivity to cytotoxic radiotherapy. Therefore, the role of CSCs in tumor formation, development and response to anti-tumor therapies is at present under intense investigation.
In this research topic, we aim to analyze the variety of factors associated with tumor insensitivity to ionizing radiation. We welcome contributions that highlight the following aspects of this subject area:

- Intracellular and intratumoral molecular events associated with radiation resistance;
- Metabolic perturbations in radioresistant carcinoma cells;
- Cancer stem cells (CSC): CSC plasticity, crosstalk with other tumor cells (non-CSCs, fibroblasts, immune system cells, etc.);
- Role of microenvironmental factors In tumor insensitivity to ionizing radiation;
- Molecular biomarkers to predict radiation resistance;
- Molecular targets (including imaging) to improve radiation tumor response;
- Chemical compounds for combination with ionizing radiation;
- Translational research on radiation oncology.