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      Progression in low‐intensity ultrasound‐induced tumor radiosensitization

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          Abstract

          Background

          Radiotherapy (RT) is a widely utilized tumor treatment approach, while a significant obstacle in this treatment modality is the radioresistance exhibited by tumor cells. To enhance the effectiveness of RT, scientists have explored radiosensitization approaches, including the use of radiosensitizers and physical stimuli. Nevertheless, several approaches have exhibited disappointing results including adverse effects and limited efficacy. A safer and more effective method of radiosensitization involves low‐intensity ultrasound (LIUS), which selectively targets tumor tissue and enhances the efficacy of radiation therapy.

          Methods

          This review summarized the tumor radioresistance reasons and explored LIUS potential radiosensitization mechanisms. Moreover, it covered diverse LIUS application strategies in radiosensitization, including the use of LIUS alone, ultrasound‐targeted intravascular microbubble destruction, ultrasound‐mediated targeted radiosensitizers delivery, and sonodynamic therapy. Lastly, the review presented the limitations and prospects of employing LIUS‐RT combined therapy in clinical settings, emphasizing the need to connect research findings with practical applications.

          Results and Conclusion

          LIUS employs cost‐effective equipment to foster tumor radiosensitization, curtail radiation exposure, and elevate the quality of life for patients. This efficacy is attributed to LIUS's ability to utilize thermal, cavitation, and mechanical effects to overcome tumor cell resistance to RT. Multiple experimental analyses have underscored the effectiveness of LIUS in inducing tumor radiosensitization using diverse strategies. While initial studies have shown promising results, conducting more comprehensive clinical trials is crucial to confirm its safety and effectiveness in real‐world situations.

          Abstract

          This review summaries the tumor radioresistance reasons and explores LIUS potential radiosensitization mechanisms. Moreover, it covers diverse LIUS application strategies in radiosensitization, including the use of LIUS alone, ultrasound‐targeted intravascular microbubble destruction, ultrasound‐mediated targeted radiosensitizers delivery, and sonodynamic therapy. Lastly, the review presents the limitations and prospects of employing LIUS‐RT combined therapy in clinical settings, emphasizing the need to connect research findings with practical applications.

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          Most cited references121

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          Cancer and Radiation Therapy: Current Advances and Future Directions

          In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.
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            Multifunctional sonosensitizers in sonodynamic cancer therapy

            Phototherapy, including photodynamic therapy and photothermal therapy, has the potential to treat several types of cancer. Phototherapy, including photodynamic therapy and photothermal therapy, has the potential to treat several types of cancer. However, to be an effective anticancer treatment, it has to overcome limitations, such as low penetration depth, low target specificity, and resistance conferred by the local tumor microenvironment. As a non-invasive technique, low-intensity ultrasound has been widely used in clinical diagnosis as it exhibits deeper penetration into the body compared to light. Recently, sonodynamic therapy (SDT), a combination of low-intensity ultrasound with a chemotherapeutic agent (sonosensitizer), has been explored as a promising alternative for cancer therapy. As all known cancer treatments such as chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, and drug delivery have been advanced independently enough to complement others substantially, the combination of these therapeutic modalities with SDT is opportune. This review article highlights the recent advances in SDT in terms of sonosensitizers and their formulations and anticancer therapeutic efficacy. Also discussed is the potential of SDT in combination with other modalities to address unmet needs in precision medicine.
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              NF-κB, an active player in human cancers.

              NF-κB comprises a family of five transcription factors that form distinct protein complexes, which bind to consensus DNA sequences at promoter regions of responsive genes regulating cellular processes. The past three decades have witnessed remarkable progress in understanding the NF-κB signaling pathway in physiologic and pathologic conditions. The role of NF-κB in human cancer initiation, development, metastasis, and resistance to treatment has drawn particular attention. A significant number of human cancers have constitutive NF-κB activity due to the inflammatory microenvironment and various oncogenic mutations. NF-κB activity not only promotes tumor cells' proliferation, suppresses apoptosis, and attracts angiogenesis, but it also induces epithelial-mesenchymal transition, which facilitates distant metastasis. In certain circumstances, NF-κB activation may also remodel local metabolism and anergize the immune system to favor tumor growth. Suppression of NF-κB in myeloid cells or tumor cells usually leads to tumor regression, which makes the NF-κB pathway a promising therapeutic target. However, because of its vital role in various biologic activities, components of the NF-κB pathway need to be carefully selected and evaluated to design targeted therapies.
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                Author and article information

                Contributors
                zhiyi_chen@usc.edu.cn
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                05 July 2024
                July 2024
                : 13
                : 13 ( doiID: 10.1002/cam4.v13.13 )
                : e7332
                Affiliations
                [ 1 ] Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, The Affiliated Changsha Central Hospital, Hengyang Medical School University of South China Changsha Hunan Province China
                [ 2 ] Institute of Medical Imaging, Hengyang Medical School, University of South China Hengyang Hunan Province China
                [ 3 ] The Seventh Affiliated Hospital, Hunan Veterans Administration Hospital, Hengyang Medical School University of South China Changsha Hunan Province China
                Author notes
                [*] [* ] Correspondence

                Zhiyi Chen, Key Laboratory of Medical Imaging Precision Theranostics and Radiation Protection, College of Hunan Province, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, Hunan Province, China.

                Email: zhiyi_chen@ 123456usc.edu.cn

                Author information
                https://orcid.org/0000-0002-5973-4522
                Article
                CAM47332 CAM4-2024-01-0518.R1
                10.1002/cam4.7332
                11224918
                38967145
                402e1e79-f632-4846-a424-048d73410d6a
                © 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 May 2024
                : 25 January 2024
                : 10 May 2024
                Page count
                Figures: 4, Tables: 1, Pages: 16, Words: 10800
                Funding
                Funded by: Key R&D Program of Hunan Province
                Award ID: 2021SK2035
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81971621
                Award ID: 82102087
                Award ID: 82272028
                Funded by: Natural Science Foundation of Hunan Province , doi 10.13039/501100004735;
                Award ID: 2022JJ30039
                Award ID: 2022JJ40392
                Funded by: Project of Science and Technology Innovation of Hunan Province
                Award ID: 2021SK51807
                Categories
                Review
                Review
                Custom metadata
                2.0
                July 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.5 mode:remove_FC converted:05.07.2024

                Oncology & Radiotherapy
                bioeffects,low‐intensity ultrasound,mechanism,radiosensitization,tumor treatment

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