Kumar Bishnupuri1*
Shuyu Zhang2,3,4,5- 1Washington University School of Medicine, St. Louis, MO, United States
- 2The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China
- 3Laboratory of Radiation Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
- 4Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China
- 5National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, China
Editorial on the Research Topic:
Regulators of radiosensitivity in colorectal cancer
Ionizing radiation has been used for the treatment of cancer since 1896, shortly after Roentgen’s discovery of X-rays (1). The term ‘radiosensitivity’ is one of the most extensively used words in oncology. It was initially used by French as “radiosensibilité” and by Germans as “Strahlenempfindlichkeit” in 1907 (2). The French “radiosensibilité” was likely originated from “radioactivité”, proposed by Curie to replace the term “hyper-phosphorescence” initially chosen by Becquerel following his discovery of natural radioactivity in 1896. While the term “radiosensitivity” was used by the pioneers to describe only the predisposition to the radiation-induced adverse tissue reactions related to cell death, a confusion emerged in the literature from the 1930s when English became the official language during the first International Congresses of Radiology, and the term “radiosensitivity” was indifferently used to describe the toxic, cancerous, or aging effect of irradiation (3). Accordingly, the mechanism of radiosensitivity, notably observed after radiotherapy appeared to be different than those linked to predisposition to radiation-induced cancer, commonly termed as radiosusceptibility. The separate use of the terms ‘radiosensitivity’ and ‘radiosusceptibility’ has been suggested to describe variability in the risk of, respectively, adverse tissue reactions (deterministic effect) following radiotherapy and radiation-induced cancer (stochastic effect).
Cancer cells respond to irradiation in a heterogeneous manner depending on their intrinsic properties for regulating their DNA damage repairs, mitochondrial functions, distribution of cells in different phases of the cell cycle, and tendency to undergo apoptosis. Furthermore, extrinsic environment such as the degree of hypoxia within the tumor population is also an important factor for regulating response of cancer cells to radiotherapy (RT). In addition, the degree of radiosensitivity of cancer cells depends on the cell heterogeneity within the tumor mass that includes cancer-initiating cells or cancer stem cells. In recent years, researchers in oncology identified potential genes, miRNAs, RNA-binding proteins, and stem cells-associated factors regulating the radiosensitivity of cancer cells, hence the overall effectiveness of radiotherapy.
Radiotherapy is a standard treatment for solid tumors and over 50% of patients with cancer receive irradiation as therapy. While radiotherapy has significantly improved the overall survival and quality of life of cancer patients, its efficacy has still been markedly limited by radioresistance in a significant number of cancer patients, resulting in failure of the radiotherapeutic control of the disease. Radioresistance leads to cancer recurrence, metastasis, and poor prognosis of cancer patients, hence constitutes a substantial barrier to the success in cancer management. Accordingly, understanding the molecular mechanisms that underlie both intrinsic and acquired radioresistance to cancer cells is extremely important to develop effective treatments to overcome the malignancy permanently.
One of the major problems linked to the current is the fact that they are optimized for decreasing tumor in bulk by acting mainly on the non-stem cancer cells while leaving cancer stems cells (CSCs) untouched. Moreover, these cancer cells have been demonstrated to be highly resistant to cancer treatments, owing to different intrinsic characteristics typical to these cells. CSCs have an important role in acquired resistance too, that develops because of cancer treatments and has been associated with different biological processes. Asymmetric division of cancer treatment-resistant CSCs contribute to cell heterogeneity within the tumor and increase the abundance of the CSC population (4, 5). In addition, the tumor microenvironment plays an important role in the acquisition of radioresistance. Some immune cells, cancer-associated fibroblasts (CAFs) and even adipocytes contribute to the development of a resistant phenotype through the production of several soluble factors, such as cytokines, chemokines, and metabolites (6), which stimulate molecular mechanisms involved in the development of a radioresistant phenotype.
Overall, radiosensitivity of cancer cells, in a broader spectrum, provides a fundamental basis of cancer treatment management. This Research Topic of the ‘Frontiers in Oncology’ journal is focused on defining/identifying biological factors both within the tumor and in the surrounding microenvironment regulating cell cycle, oxidative stress, hypoxia, apoptosis, DNA damage/repair, mitochondrial function, inflammation, and stem cell survival with a broader aim to expand our knowledge of cancer cell radiosensitivity, and its implication in improving cancer patient outcomes.
Author contributions
KB: Conceptualization and writing; SZ: Writing. All authors contributed to the article and approved the submitted version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
1. Connell PP, Hellman S. Advances in radiotherapy and implications for the next century: A historical perspective. Cancer Res (2009) 69(2):383–92. doi: 10.1158/0008-5472.CAN-07-6871
2. Britel M, Bourguignon M, Foray N. The use of the term ‘radiosensitivity’ through history of radiation: From clarity to confusion. Int J Radiat Biol (2018) 94:503–12. doi: 10.1080/09553002.2018.1450535
3. Foray N, Bourguignon M, Hamada N. Individual response to ionizing radiation. Mutat Res Reviews Mutat Res (2016) 770:369–86. doi: 10.1016/j.mrrev.2016.09.001
4. Sato K, Shimokawa T, Imai T. Difference in acquired radioresistance induction between repeated photon and particle irradiation. Front Oncol (2019) 9:1213. doi: 10.3389/fonc.2019.01213
5. 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(8):1301–15. doi: 10.1080/09553002.2022.2047825
Keywords: irradiation, radiosusceptibility, radiotherapy, resistance, survival
Citation: Bishnupuri K and Zhang S (2022) Editorial: Regulators of radiosensitivity in colorectal cancer. Front. Oncol. 12:1094238. doi: 10.3389/fonc.2022.1094238
Received: 09 November 2022; Accepted: 10 November 2022;
Published: 29 November 2022.
Edited and Reviewed by:
Liang Qiao, Westmead Institute for Medical Research, AustraliaCopyright © 2022 Bishnupuri and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Kumar Bishnupuri, kbishnup@wustl.edu