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      Molecular mechanisms of tumor resistance to radiotherapy

      review-article
      Author(s): 1 , 2 , 1 , 1 , 2 , 1 , 3 ,
      Publication date (Electronic):
      Journal: Molecular Cancer
      Publisher: BioMed Central
      Keywords: Cancer, Radiotherapy, Tumor resistance

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          Abstract

          Background

          Cancer is the most prevalent cause of death globally, and radiotherapy is considered the standard of care for most solid tumors, including lung, breast, esophageal, and colorectal cancers and glioblastoma. Resistance to radiation can lead to local treatment failure and even cancer recurrence.

          Main body

          In this review, we have extensively discussed several crucial aspects that cause resistance of cancer to radiation therapy, including radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance of cancer stem cells, modification of cancer cells and their microenvironment, presence of exosomal and non-coding RNA, metabolic reprogramming, and ferroptosis. We aim to focus on the molecular mechanisms of cancer radiotherapy resistance in relation to these aspects and to discuss possible targets to improve treatment outcomes.

          Conclusions

          Studying the molecular mechanisms responsible for radiotherapy resistance and its interactions with the tumor environment will help improve cancer responses to radiotherapy. Our review provides a foundation to identify and overcome the obstacles to effective radiotherapy.

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          Most cited references172

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
          Article 0 comments Cited 32053 times – based on 0 reviews     Review now
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            Cancer statistics, 2023

            Rebecca L Siegel, Kimberly D Miller, Nikita Sandeep Wagle … (2023)
            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.
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              Hallmarks of Cancer: New Dimensions

              Douglas Hanahan (2022)
              The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
              Article 0 comments Cited 1930 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yu Wu:
                ORCID: http://orcid.org/0000-0002-6952-1774
                wagd5132@163.com
                Yingqiu Song:
                ORCID: http://orcid.org/0000-0003-0678-9981
                syq18900917411@163.com
                Runze Wang:
                ORCID: http://orcid.org/0009-0008-8383-9595
                wrzz999@163.com
                Tianlu Wang:
                ORCID: http://orcid.org/0000-0002-9732-3441
                wangtianlu@cancerhosp-ln-cmu.com
                Journal
                Journal ID (nlm-ta): Mol Cancer
                Journal ID (iso-abbrev): Mol Cancer
                Title: Molecular Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1476-4598
                Publication date (Electronic): 15 June 2023
                Publication date PMC-release: 15 June 2023
                Publication date Collection: 2023
                Volume: 22
                Electronic Location Identifier: 96
                Affiliations
                [1 ]GRID grid.459742.9, ISNI 0000 0004 1798 5889, Department of Radiotherapy, , Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, ; No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042 Liaoning Province China
                [2 ]GRID grid.411971.b, ISNI 0000 0000 9558 1426, School of Graduate, , Dalian Medical University, ; Dalian, 116044 China
                [3 ]GRID grid.30055.33, ISNI 0000 0000 9247 7930, Faculty of Medicine, , Dalian University of Technology, ; Dalian, 116024 China
                Author information
                http://orcid.org/0000-0002-6952-1774
                http://orcid.org/0000-0003-0678-9981
                http://orcid.org/0009-0008-8383-9595
                http://orcid.org/0000-0002-9732-3441
                Article
                Publisher ID: 1801
                DOI: 10.1186/s12943-023-01801-2
                PMC ID: 10268375
                PubMed ID: 37322433
                SO-VID: 437442c1-b4a7-4b6e-85f3-bd302af82d68
                Copyright © © The Author(s) 2023
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 3 January 2023
                Date accepted : 3 June 2023
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © BioMed Central Ltd., part of Springer Nature 2023

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer,radiotherapy,tumor resistance
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer, radiotherapy, tumor resistance

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