MOLECULAR MECHANISMS UNDERLYING CANCER CELL RADIORESISTANCE
Keywords:
ionizing radiation, DNA repair, cell cycle, proliferation, radiotherapy
Abstract
Radioresistance of the tumor cells remains a significant obstacle for the radiotherapy treatment of cancer. Radioresistance involves multiple genes, factors, and mechanisms that adapt cancer cells or tissues to radiotherapy-induced changes and develop resistance to ionizing radiation. The major studies of the effect of radiation on cells reported include the following areas: 1) the study of DNA damages and their repair; 2) mutations in tumor suppressor genes and radiation-induced oncogene expression; 3) the role of growth factors and cytokines; 4) violation of the cell cycle; 5) elucidation of the mechanisms of apoptosis and necrosis. This review aimed to provide a theoretical basis, which may improve the sensitivity of cancer cells to radiotherapy. It focuses on the roles of tumor metabolism, DNA repair capacity, cell cycle checkpoints, and the tumor microenvironment in the development of radioresistance of cancer cells. Understanding the molecular alterations that lead to radioresistance may provide new diagnostic markers and therapeutic targets to improve radiotherapy efficacy.
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4. Bencokova, Z., Kaufmann, M. R., Pires, I. M., Lecane, P. S., Giaccia, A. J., & Hammond, E. M. (2009). ATM activation and signaling under hypoxic conditions. Molecular and cellular biology, 29(2), 526–537. https://doi.org/10.1128/MCB.01301-08
5. Bhatt, A. N., Chauhan, A., Khanna, S., Rai, Y., Singh, S., Soni, R., Kalra, N., & Dwarakanath, B. S. (2015). Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells. BMC cancer, 15, 335. https://doi.org/10.1186/s12885-015-1368-9
6. Brandsma, I., & Gent, D. C. (2012). Pathway choice in DNA double strand break repair: observations of a balancing act. Genome integrity, 3(1), 9. https://doi.org/10.1186/2041-9414-3-9
7. Brown, J. M., Recht, L., & Strober, S. (2017). The Promise of Targeting Macrophages in Cancer Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research, 23(13), 3241–3250. https://doi.org/10.1158/1078-0432.CCR-16-3122
8. Buscemi, G., Savio, C., Zannini, L., Miccichè, F., Masnada, D., Nakanishi, M., Tauchi, H., Komatsu, K., Mizutani, S., Khanna, K., Chen, P., Concannon, P., Chessa, L., & Delia, D. (2001). Chk2 activation dependence on Nbs1 after DNA damage. Molecular and cellular biology, 21(15), 5214–5222. https://doi.org/10.1128/MCB.21.15.5214-5222.2001
9. Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D. (2000). Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes & development, 14(3), 278–288.
10. Chen, Y., Li, Z., Dong, Z., Beebe, J., Yang, K., Fu, L., & Zhang, J. T. (2017). 14-3-3σ Contributes to Radioresistance By Regulating DNA Repair and Cell Cycle via PARP1 and CHK2. Molecular cancer research : MCR, 15(4), 418–428. https://doi.org/10.1158/1541-7786.MCR-16-0366
11. Chevalier, F., Hamdi, D. H., Saintigny, Y., & Lefaix, J. L. (2015). Proteomic overview and perspectives of the radiation-induced bystander effects. Mutation research. Reviews in mutation research, 763, 280–293. https://doi.org/10.1016/j.mrrev.2014.11.008
12. Chu, T. Y., Yang, J. T., Huang, T. H., & Liu, H. W. (2014). Crosstalk with cancer-associated fibroblasts increases the growth and radiation survival of cervical cancer cells. Radiation research, 181(5), 540–547. https://doi.org/10.1667/RR13583.1
13. Chung, F. Y., Huang, M. Y., Yeh, C. S., Chang, H. J., Cheng, T. L., Yen, L. C., Wang, J. Y. & Lin, S. R. (2009). GLUT1 gene is a potential hypoxic marker in colorectal cancer patients. BMC Cancer, 9, 241. https://doi.org/10.1186/1471-2407-9-241
14. Cook, P. J., Thomas, R., Kingsley, P. J., Shimizu, F., Montrose, D. C., Marnett, L. J., Tabar, V. S., Dannenberg, A. J., & Benezra, R. (2016). Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma. Neuro-oncology, 18(10), 1379–1389. https://doi.org/10.1093/neuonc/now049
15. Dasika, G. K., Lin, S. C., Zhao, S., Sung, P., Tomkinson, A., & Lee, E. Y. (1999). DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene, 18(55), 7883–7899. https://doi.org/10.1038/sj.onc.1203283
16. De Schutter, H., Landuyt, W., Verbeken, E., Goethals, L., Hermans, R., & Nuyts, S. (2005). The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy +/- chemotherapy. BMC cancer, 5, 42. https://doi.org/10.1186/1471-2407-5-42
17. Dehne, N., Mora, J., Namgaladze, D., Weigert, A., & Brüne, B. (2017). Cancer cell and macrophage cross-talk in the tumor microenvironment. Current opinion in pharmacology, 35, 12–19. https://doi.org/10.1016/j.coph.2017.04.007
18. Erenpreisa, J., Cragg, M. S. (2001). Mitotic death: a mechanism of survival? A review. Cancer Cell International, 1(1), 1–7. https://doi.org/10.1186/1475-2867-1-1
19. Falcicchio, M., Ward, J. A., Macip, S. & Doveston, R. G. (2020). Regulation of p53 by the 14-3-3 protein interaction network: new opportunities for drug discovery in cancer. Cell Death Discovery, 6, 126. https://doi.org/10.1038/s41420-020-00362-3
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Published
2022-01-17
How to Cite
Chorna, I. (2022). MOLECULAR MECHANISMS UNDERLYING CANCER CELL RADIORESISTANCE. Scientific Journal of Polonia University, 48(5), 142-151. https://doi.org/10.23856/4818
Section
HEALTH, ENVIRONMENT, DEVELOPMENT
