1. Sung H, Filho AM, Laversanne M, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries. CA Cancer J Clin. 2026;76:e70090. doi: 10.3322/caac.70090. PMID: 42417444; PMCID: PMC13343830.
2. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12-49. doi: 10.3322/caac.21820. PMID: 38230766.
3. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394:1467-80. doi: 10.1016/s0140-6736(19)32319-0. PMID: 31631858.
4. Benson AB, Venook AP, Al-Hawary MM, Azad N, Chen YJ, Ciombor KK, et al. Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20:1139-67. doi: 10.6004/jnccn.2022.0051. PMID: 36240850.
5. Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv22-iv40. doi: 10.1093/annonc/mdx224. PMID: 28881920.
6. Citrin DE. Recent developments in radiotherapy. N Engl J Med. 2017;377:1065-75. doi: 10.1056/NEJMra1608986. PMID: 28902591.
7. Barker HE, Paget JT, Khan AA, Harrington KJ. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer. 2015;15:409-25. doi: 10.1038/nrc3958. PMID: 26105538; PMCID: PMC4896389.
8. Alamilla-Presuel JC, Burgos-Molina AM, González-Vidal A, Sendra-Portero F, Ruiz-Gómez MJ. Factors and molecular mechanisms of radiation resistance in cancer cells. Int J Radiat Biol. 2022;98:1301-15. doi: 10.1080/09553002.2022.2047825. PMID: 35225732.
9. Wang Y, Liu Z, Lv Y, Long J, Lu Y, Huang P. Mechanisms of radioresistance and radiosensitization strategies for triple negative breast cancer. Transl Oncol. 2025;55:102351. doi: 10.1016/j.tranon.2025.102351. PMID: 40112501; PMCID: PMC11964565.
10. Yi J, Zhu J, Zhao C, Kang Q, Zhang X, Suo K, et al. Potential of natural products as radioprotectors and radiosensitizers: opportunities and challenges. Food Funct. 2021;12:5204-18. doi: 10.1039/d1fo00525a. PMID: 34018510.
11. Abdollahi A, Imani A, Rassouli FB. Natural radiosensitizers in cancer therapy: Mechanisms, radioresistance modulation, and translational prospects. Biochim Biophys Acta Rev Cancer. 2026;1881:189628. doi: 10.1016/j.bbcan.2026.189628. PMID: 42235835.
12. Pezzani R, Jiménez-Garcia M, Capó X, Sönmez Gürer E, Sharopov F, Rachel TYL, et al. Anticancer properties of bromelain: State-of-the-art and recent trends. Front Oncol. 2022;12:1068778. doi: 10.3389/fonc.2022.1068778. PMID: 36698404; PMCID: PMC9869248.
13. Forootan M, Amiri MM, Darvishi M, Sherwin CM, Ghanadi K. The therapeutic effects of bromelain against colorectal cancer: A systematic review. Current Cancer Therapy Reviews. 2024;20(4):402-9. doi: 10.2174/0115733947253563230922092456.
14. Mekkawy MH, Fahmy HA, Nada AS, Ali OS. Study of the radiosensitizing and radioprotective efficacy of bromelain (a pineapple extract): In vitro and in vivo. Integr Cancer Ther. 2020;19:1534735420950468. doi: 10.1177/1534735420950468. PMID: 32783540; PMCID: PMC7425266.
15. Brix N, Samaga D, Belka C, Zitzelsberger H, Lauber K. Analysis of clonogenic growth in vitro. Nat Protoc. 2021;16(11):4963-91. doi: 10.1038/s41596-021-00615-0. PMID: 34697469.
16. Doherty A, Bryce SM, Bemis JC. Chapter 6 - The In Vitro Micronucleus Assay. In: Proudlock R, editor. Genetic Toxicology Testing. Boston: Academic Press; 2016.p.161-205.
17. Bendou O, Gutiérrez-Fernández I, Marcos-Barbero EL, Bueno-Ramos N, González-Hernández AI, Morcuende R, et al. Theoretical and experimental considerations for a rapid and high throughput measurement of catalase in vitro. Antioxidants (Basel). 2021;11. doi: 10.3390/antiox11010021. PMID: 35052525; PMCID: PMC8773236.
18. Engelbrecht I, Horn S, Giesy JP, Pieters R. Determining superoxide dismutase content and catalase activity in mammalian cell lines. MethodsX. 2023;11:102395. doi: 10.1016/j.mex.2023.102395. PMID: 37791011; PMCID: PMC10542938.
19. Sommer S, Buraczewska I, Kruszewski M. Micronucleus assay: The state of art, and future directions. Int J Mol Sci. 2020;21. doi: 10.3390/ijms21041534. PMID: 32102335; PMCID: PMC7073234.
20. Fenech M, Knasmueller S, Bolognesi C, Holland N, Bonassi S, Kirsch-Volders M. Micronuclei as biomarkers of DNA damage, aneuploidy, inducers of chromosomal hypermutation and as sources of pro-inflammatory DNA in humans. Mutat Res Rev Mutat Res. 2020;786:108342. doi: 10.1016/j.mrrev.2020.108342. PMID: 33339572.
21. Chang TC, Wei PL, Makondi PT, Chen WT, Huang CY, Chang YJ. Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy. PLoS One. 2019;14:e0210274. doi: 10.1371/journal.pone.0210274. PMID: 30657763; PMCID: PMC6338369.
22. Romano B, Fasolino I, Pagano E, Capasso R, Pace S, De Rosa G, et al. The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects. Mol Nutr Food Res. 2014;58:457-65. doi: 10.1002/mnfr.201300345. PMID: 24123777.
23. Dweh TJ, Taye M, Deka D, Samanta SK, Talukdar NC. Phytochemicals as radioprotective and radiosensitizing agents in cancer radiotherapy: Advances, challenges, and future perspectives. Planta Med. 2026;92:11-32. doi: 10.1055/a-2654-6072. PMID: 41086865.
24. Haddad Zahmatkesh M, Pourafrasiabi Y, Saeidi Saedi H. Quercetin enhances radiosensitivity in T47D breast cancer cells: impact on DNA damage, clonogenic survival, and antioxidant defenses. Journal of Current Oncology and Medical Sciences. 2026;6(1):1355-62.
25. Haddad Zahmatkesh M, Vojdanpour M, Saeidi Saedi H. Bromelain as a natural radiosensitizer in MCF-7 breast cancer cells: Effects on DNA damage, clonogenic survival, and oxidative stress. Research Journal of Pharmacognosy. 2026;13(4):7-15. doi: 10.22127/rjp.2026.566591.3064.
26. Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11:239-53. doi: 10.1038/nrc3007. PMID: 21430696.
27. Chen YH, Wei MF, Wang CW, Lee HW, Pan SL, Gao M, et al. Dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor is an effective radiosensitizer for colorectal cancer. Cancer Lett. 2015;357:582-90. doi: 10.1016/j.canlet.2014.12.015. PMID: 25497009.
28. Nahum AE. The radiobiology of hypofractionation. Clin Oncol (R Coll Radiol). 2015;27(5):260-9. doi: 10.1016/j.clon.2015.02.001. PMID: 25797579.
29. Brand DH, Kirby AM, Yarnold JR, Somaiah N. How low can you go? The radiobiology of hypofractionation. Clin Oncol (R Coll Radiol). 2022;34:280-7. doi: 10.1016/j.clon.2022.02.009. PMID: 35260319.
30. Sies H. Oxidative stress: Concept and some practical aspects. Antioxidants (Basel). 2020;9. doi: 10.3390/antiox9090852. PMID: 32927924; PMCID: PMC7555448.
31. Srinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD. ROS and the DNA damage response in cancer. Redox Biol. 2019;25:101084. doi: 10.1016/j.redox.2018.101084. PMID: 30612957; PMCID: PMC6859528.
32. Sisakht M, Darabian M, Mahmoodzadeh A, Bazi A, Shafiee SM, Mokarram P, et al. The role of radiation induced oxidative stress as a regulator of radio-adaptive responses. Int J Radiat Biol. 2020;96:561-76. doi: 10.1080/09553002.2020.1721597. PMID: 31976798.
33. Zhang J, Wang X, Vikash V, Ye Q, Wu D, Liu Y, et al. ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev. 2016;2016:4350965. doi: 10.1155/2016/4350965. PMID: 26998193; PMCID: PMC4779832.