Background: Radiation therapy has become a common therapy for cancer patients and
largely improved therapeutic outcomes. However, recurrence after radiation therapy is still a major
unsolved concern of cancer patients. The Cancer Stem Cells (CSCs), a small sub-population with the
capacity of self-renewal and differentiation into diverse types of cancer cells, are considered as strong
drivers of metastasis, resistance, and recurrence.
Objective: We overview the mechanisms behind the radiation resistance of CSCs, and introduce recent
patents with the potential to overcome such an obstacle. In this review article, we will introduce those
patented compounds as potential combinatory drugs for radiation therapy and present their specific
Method: From a thorough literature review on the mechanisms of radiation resistance exhibited by
CSCs, several patents that have disclosed novel compounds or their specific applications for improving
radiation therapy will be introduced with their developmental status and experimental results.
Results: Recent studies have focused on revealing the molecular mechanisms of CSC contributing to
radiation resistance and succeeded to discover that CSCs possess intrinsic and extrinsic resistance by
preventing radiation-induced cellular damages and by adapting to the changes occurred by radiation
exposure, respectively. Among currently discovered resistant mechanisms of CSCs, DNA repair and
redox system directly decrease radiation-induced DNA breaks and relieve cellular stress caused by
Reactive Oxygen Species (ROS). Indirectly, altered metabolism and cellular signaling may help CSCs
adapt to the desolate microenvironment disrupted by radiation exposure. In order to overcome this obstacle
on the road to the efficient cancer treatment, diverse therapeutic strategies using anti-sense oligonucleotides,
small molecule inhibitors and antibodies have been tested and some of them actually
showed an efficacy on improving current radiation therapy.
Conclusion: Many agents that directly or indirectly sensitize CSCs have been developed and some of
them are on clinical trial. We expect that they will be used to enhance clinical radiation therapy in the