Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

• Main Authors: Byeong Mo Kim, Yunkyung Hong, Seunghoon Lee, Pengda Liu, Ji Hong Lim, Yong Heon Lee, Tae Ho Lee, Kyu Tae Chang, Yonggeun Hong
• Format: Article
• Language: English
• Published: MDPI AG 2015-11-01
• Series: International Journal of Molecular Sciences
• Subjects: cancer therapy; ionizing radiation (IR); resistance; cell death; DNA damage; prognostic markers; therapeutic targets
• Online Access: http://www.mdpi.com/1422-0067/16/11/25991

Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.