Strategies to Tackle Radiation Resistance by Penetrating Cancer Stem Cell Line of Scrimmage

Abstract

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 molecular mechanisms.

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 future.

Keywords: Cancer stem cell; DNA repair; hypoxia; microenvironment; radio-resistance; reactive oxygen species.