Role of DNA damage and repair in radiation cancer therapy: a current update and a look to the future

Abstract

Radiation Therapy (RT), a widely used modality against cancer, depends its effectiveness on three pillars: tumor targeting precision, minimum dose determination and co-administrated agents. The underlying biological processes of the latter two pillars are DNA damage and repair. Hopefully, Radiation treatment has nowadays been improved a lot, in terms of tumor targeting precision as well as in minimization of side effects, by reducing normal tissue radiation exposure and therefore its occurred toxicity. Normal tissue toxicity is a major risk factor for induction of genomic instability which may lead to secondary cancer development, due to the radiation therapy itself. We discuss, in this review, the biological significance of IR-induced complex DNA damage, which is currently accepted as the definite regulator of biological response to radiation, as well as the regulator of the implications of this IR signature in radiation therapy. We unite accumulating evidence and knowledge over the last 20 years or so on the importance of radiation treatment of cancer. This radiation-based therapy comes unfortunately with a deficit and this is the radiation-induced genetic instability which can fuel radiation toxicity, even several years after the initial treatment on patients through the activation of DNA damage response (DDR) and the immune system.

Keywords:

• Radiation therapy
• oxidative stress
• DNA damage and repair
• tumor resistance
• synthetic lethality
• systemic effects

Acknowledgments

We thank Prof Alexandros Georgakilas (National Technical University of Athens) for critical reading of the manuscript.

Author contributions

L.C. had the conception, supervised and commented this work; J.L. wrote the manuscript with input from all authors; J.L., K.B., R.Y. and H.L. reviewed the literature; Z.N. proofed the language, commented the article and performed its revision according to the referees’ comments.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning” in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (IKY).

Notes on contributors

Jingya Liu

Jingya Liu, BSc in nursing, graduated from Hebei Union University in 2012, currently working in the Department of Neurosurgery, Tangshan Workers' Hospital, Hebei Province, as a nurse in charge. She has been engaged in NCU intensive care unit nursing work for 14 years, has rich intensive care unit nursing work experience, and she is an expert rescuing trainer of critically ill patients and brain surgery patients.

Kun Bi

Kun Bi, BSc, graduated from Chengde Medical College in 1999 and is currently working in the Department of Neurosurgery of Tangshan Workers' Hospital. He is an attending physician and has been engaged in neurosurgery for more than 20 years. Experienced at surgery for skull base tumors, spinal cord tumors, and cerebrovascular diseases.

Run Yang

Run Yang, in 1995, she graduated from the Second Military Medical University, Nanjing Military Medical College, from the Department of Nursing; in 2001, she graduated from the Second Military Medical University, from the Nanjing Military Medical College, from the College of Pharmacy; in 2012, she graduated from Shandong University, majoring in nursing. From 1995 to 2006, she worked in the Hospital of the Fifth Division of the Naval Air Force of the North Sea Fleet, in the outpatient department, as a nurse; from 2006 to present, she worked in the medical examination center of Yantai Infectious Disease Hospital as a nurse in charge.

Hongxia Li

Hongxia Li, graduated from Qingdao University School of Medicine in 1997 with a junior college major in nursing, and graduated from a technical secondary school in 2006 with a major in nursing from Shandong University. From 1991 to 2007, she worked in the operating room of the ward of Yantaishan Hospital, Yantai City, as the chief nurse. Since 2007, she works in the interventional operating room of Yantaishan Hospital, Yantai City as the chief nurse.

Zacharenia Nikitaki

Zacharenia Nikitaki, since 2017 is a post-doctoral research associate at the DNA Damage Lab of the National Technical University of Athens (NTUA), Greece. She holds a PhD in Radiobiology, an MSc in Nanotechnology and an MSc in Applied Physics, all received from NTUA.

Li Chang

Li Chang, born on February 25, 1970, is a head nurse. She graduated from the Affiliated Health School of Liaoning Traditional Chinese Medicine in 1988, graduated from Tongji University in 2001, and serves as the head nurse since 2004. During her tenure as the head nurse, she worked in pediatrics, general surgery, cardiovascular surgery, interventional, anorectal surgery, outpatient, neurosurgery.