Scientific Online Resource System

Varna Medical Forum

Radiotherapy and cell death. Significance of cell death patterns in the radiotherapy of cancer patients

Temenuzhka Radeva-Petkova, Elitsa Encheva, Ivan Donev, Yavor Kashlov


Radiotherapy is one of the three main treatment modalities of cancer, together with surgery and chemotherapy. It is applied to 50% - 60% of all cancer patients at a certain stage of their complex treatment, and in more than half of the patients radiotherapy is used with radical intent. The main goal is to deliver a high dose of radiation to the tumor, while maintaining an acceptable dose to adjacent tissues. The development of modern radiotherapy techniques - 3D conformal radiotherapy, intensity-modulated radiotherapy (IMRT), image-guided radiation therapy (IGRT), leads to significant advances in the therapeutic results. Nevertheless it is still not clear why some tumors are sensitive and others are resistant to irradiation. The main target of ionizing radiation is DNA. By direct and indirect action, ionizing radiation induces structural changes in DNA and cell death. Cell death is equivalent to any process that leads to loss of mitotic activity. The mechanism of radiation-induced cell death has not been fully understood yet. There are many studies that reveal a number of signaling pathways and their role in inducing radiation resistance and sensitivity, respectively. Finding the exact mechanisms of cell death will allow us to discover new target therapies, and combining them with radiotherapy will improve therapeutic results.


cancer; radiotherapy; cell death

Full Text


Hanahan D, Weinberg R. The hallmarks of cancer. Cell. 2000;100:57-70

Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461:1071-1078

Hall EJ. Cancer caused by x-rays-a random event?. Lancet Oncol. 2007;8:369-370

Brandsma D, Stalpers L, Taal W et al. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol. 2008;9:453-461

Emami B, Lyman J, Brown A et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109-122

Eric J. Hall, Amato J. Giaccia, Radiobiology for the Radiologist. Lippincott Williams & Wilkins 2012

Rajamanickam Baskar, Kuo Ann Lee, Richard Yeo, Kheng-Wei Yeoh, Cancer and Radiation Therapy: Current Advances and Future Directions, Int J Med Sci 2012; 9(3):193-199.

Bradly G. Wouters, Cell death after irradiation: how, when and why cells die.

Ross GM, Induction of cell death by radiotherapy, Endocr Relat Cancer. 1999 Mar;6(1):41-4.

Mo Kim B, Hong Y, Lee S et al. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy, Int J Mol Sci. 2015 Nov; 16(11): 26880-26913.

Verheij M. Clinical biomarkers and imaging for radiotherapy-induced cell death. Cancer Metastasis Rev. 2008;27:471-480

Fuentes-Raspall MJ, Caragol I, Alonso C et al. Apoptosis for prediction of radiotherapy late toxicity: lymphocyte subset sensitivity and potential effect of TP53 Arg72Pro polymorphism. 2015 Mar;20(3):371-82.

Michael JM, Lavin MF, Watters DJ. Resistance to radiation-induced apoptosis in Burkitt's lymphoma cells is associated with defective ceramide signaling. 1997 Aug 15;57(16):3600-5.

Sato N, Mizumoto K, Nakamura M. et al. A possible role for centrosome overduplication in radiation-induced cell death. Oncogene. 2000;19:5281-5290

Vakifahmetoglu H, Olsson M, Zhivotovsky B. Death through a tragedy: mitotic catastrophe. Cell Death Differ. 2008;15:1153-1162

Jonathan EC, Bernhard EJ, McKenna WG. How does radiation kill cells?. Curr Opin Chem Biol. 1999;3:77-83

Tam SY, Cheung Wu VW, and Law H. Influence of autophagy on the efficacy of radiotherapy. Radiat Oncol. 2017; 12: 57.

Daido S, Yamamoto A, Fujiwara K, Sawaya R, Kondo S, Kondo Y. Inhibition of the DNA-dependent protein kinase catalytic subunit radiosensitizes malignant glioma cells by inducing autophagy, Cancer Res. 2005 May 15;65(10):4368-75

Palumbo S, Pirtoli L, Tini P, et al. Different involvement of autophagy in human malignant glioma cell lines undergoing irradiation and temozolomide combined treatments. J Cell Biochem. 2012;113(7):2308-18.

Albert JM, Kim KW, Cao C, Lu B. Targeting the Akt/mammalian target of rapamycin pathway for radiosensitization of breast cancer. Mol Cancer Ther. 2006;5(5):1183-9.

Chen Y, Li X, Guo L et al. Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer. 2015 Aug; 12(2): 1645-1652.

Paglin S., Hollister T., Delohery T. et al. A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 2001;61:439-444.

Zhuang W, Qin Z, Liang Z. The role of autophagy in sensitizing malignant glioma cells to radiation therapy. Acta Biochim Biophys Sin (Shanghai). 2009 May; 41(5):341-51.

Wauters BG. Cell death after irradiation: how, when and why cell die. Chapter 3 Basic Clinical Radiobiology Fourth Edition 2009, Michael C. Joiner, Albert van der Kogel

Rainaldi G., Ferrante A., Indovina P.L., Santini M.T. Induction of apoptosis or necrosis by ionizing radiation is dose-dependent in MG-63 osteosarcoma multicellular spheroids. Anticancer Res. 2003;23:2505-2518.

Wen Zhou, Junying Yuan. Necroptosis in health and diseases, Semin Cell Dev Biol. 2014 Nov;35:14-23.

Lalaoui N, Lindqvist LM, Sandow JJ, Ekert PG. The molecular relationships between apoptosis, autophagy and necroptosis. Semin Cell Dev Biol 2015; 39: 63-69.

Najoua Lalaoui and Gabriela Brumatti, Relevance of necroptosis in cancer, Immunology and Cell Biology (2017) 95, 137-145 & 2017 Australasian Society for Immunology Inc. All rights reserved 0818-9641/17.

Nehs MA, Lin CI, Kozono DE et al. Necroptosis is a novel mechanism of radiation-induced cell death in anaplastic thyroid and adrenocortical cancers. Surgery. 2011 Dec; 150(6):1032-9.

Shrivastava S, Mansure JJ, Almajed W et al. Mol Cancer Ther. The Role of HMGB1 in Radioresistance of Bladder Cancer. 2016 Mar;15(3):471-9.

Wang HH, Wu ZQ, Qian D et al. Ablative Hypofractionated Radiation Therapy Enhances Non-Small Cell Lung Cancer Cell Killing via Preferential Stimulation of Necroptosis In Vitro and In Vivo, Int J Radiat Oncol Biol Phys. 2018 May 1;101(1):49-62.

K. Lauber et al, Dying cell clearance and its impact on the outcome of tumor radiotherapy, Frontiers in Oncology 2(116):116 , September 2012



Font Size