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The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence
Open accessAbstract
Radiotherapy plays a central part in curing cancer. For decades, most research on improving treatment outcomes has focused on modulating radiation-induced biological effects on cancer cells. Recently, we have better understood that components within the tumour microenvironment have pivotal roles in determining treatment outcomes. In this Review, we describe vascular, stromal and immunological changes that are induced in the tumour microenvironment by irradiation and discuss how these changes may promote radioresistance and tumour recurrence. We also highlight how this knowledge is guiding the development of new treatment paradigms in which biologically targeted agents will be combined with radiotherapy.
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“Generation of intratumoral O2 is also feasible to improve the efficacy of radiotherapy by using bioactive albumin-MnO2 nanoparticles [94].”
From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [94]
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2 retracted
RETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
Lee, K., Zhang, H., Qian, D. Z., Rey, S., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909353106 · Cited by 451
RetractedMMP-2 siRNA Inhibits Radiation-Enhanced Invasiveness in Glioma Cells
Badiga, A. V., Chetty, C., Kesanakurti, D., Are, D., Gujrati, M., Klopfenstein, J. D., Dinh, D. H., & Rao, J. S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020614 · Cited by 110
RetractedHallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Angiogenesis in cancer and other diseases
Carmeliet, P., & Jain, R. K. (2000) · Nature · doi:10.1038/35025220 · Cited by 9,070
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895
Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy
Jain, R. K. (2005) · Science · doi:10.1126/science.1104819 · Cited by 5,527
Hypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177
Flagged first, then by citations
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Sorted by citations
Items 901–1,000 of 1,005
Improved pharmaceutical research and development with AIE-based nanostructures
Zhang, Y., Wang, Y., Wang, J., & Liang, X. (2018) · Materials Horizons · doi:10.1039/c8mh00648b · Cited by 23
An orthotopic non-small cell lung cancer model for image-guided small animal radiotherapy platforms
Iglesias, V. S., van Hoof, S. J., Vaniqui, A., Schyns, L. E. J. R., Lieuwes, N. G., Yaromina, A., Spiegelberg, L., Groot, A. J., Verhaegen, F., Theys, J., et al. (2018) · British Journal of Radiology · doi:10.1259/bjr.20180476 · Cited by 23
Pancreatic Tumor Microenvironment Modulation by EphB4-ephrinB2 Inhibition and Radiation Combination
Lennon, S., Oweida, A., Milner, D. C., Phan, A. V., Bhatia, S., Court, B. V., Darragh, L. B., Mueller, A. C., Raben, D., Martinez-Torrecuadrada, J. L., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2811 · Cited by 22
Toss, M. S., Miligy, I. M., Gorringe, K. L., Al-Kawaz, A., Mittal, K., Aneja, R., Ellis, I. O., Green, A. R., Roxanis, I., & Rakha, E. A. (2019) · Modern Pathology · doi:10.1038/s41379-019-0296-7 · Cited by 24
Bychkov, M. L., Kirichenko, A. V., Shulepko, M. A., Mikhaylova, I. N., Kirpichnikov, M. P., & Lyukmanova, E. N. (2021) · Biomedicines · doi:10.3390/biomedicines9101324 · Cited by 23
Regulatory roles of phytochemicals on circular RNAs in cancer and other chronic diseases
Zhang, S., Long, F., Lin, H., Wang, X., Jiang, G., & Wang, T. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105936 · Cited by 23
Wang, W., Wang, X., Tao, F., Hu, K., Zhang, J., Wu, J., You, L., & Zhao, W. (2022) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c00432 · Cited by 23
Ali, E., Trailin, A. V., Ambrożkiewicz, F., Liška, V., & Hemminki, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315292 · Cited by 25
“The main challenge to classic radiotherapy is its side effects on the surrounding tissues [65].”
BackgroundCellular senescence in the response of HR+ breast cancer to radiotherapy and CDK4/6 inhibitors
Klapp, V., Buqué, A., Bloy, N., Sato, A., Yamazaki, T., Zhou, X. K., Formenti, S. C., Galluzzi, L., & Petroni, G. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-03964-4 · Cited by 23
Wang, Y., Meng, L., Meng, S., Huang, L., Luo, S., Wu, X., & Gong, X. (2023) · Cancer Biology & Therapy · doi:10.1080/15384047.2023.2203332 · Cited by 24
“by cell-intrinsic factors and extracellular microenvironment, particularly the immune microenvironment.(3) PD-1 expressed by immune cells can interact with PD-L1 expressed by tumor cells, which inhibits anti-tumor immunity and contributes to immune evasion.”
BackgroundZhou, D., Gao, Y., Yang, Z., Wang, N., Ge, J., Cao, X., Kou, D., Gu, Y., Li, C., Afshari, M. J., et al. (2023) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.3c03636 · Cited by 23
Lyu, M., Zhang, T., Yang, L., Xiang, J., Zhu, D., Xia, L., Guo, B., Xu, Y., Yu, H., & Tang, B. Z. (2023) · Chemical Engineering Journal · doi:10.1016/j.cej.2023.145179 · Cited by 23
Sampath, S., Won, H., Massarelli, E., Li, M., Frankel, P. H., Vora, N. L., Vora, L., Maghami, E. G., & Kortylewski, M. (2018) · Oncotarget · doi:10.18632/oncotarget.24397 · Cited by 23
“Cell death induced by ionizing radiation or certain types of chemotherapy results in release of mediators, such as cytokines, chemokines or damageassociated molecular patterns (DAMPs), which modulate activity of immune cells recruited into the tumor after treatment [8].”
BackgroundKeam, S. P., Gulati, T., Gamell, C., Caramia, F., Huang, C., Schittenhelm, R. B., Kleifeld, O., Neeson, P. J., Haupt, Y., & Williams, S. (2018) · The Prostate · doi:10.1002/pros.23500 · Cited by 23
“Overall, this is consistent with the known features of new tissue deposition and remodeling as relatively late effects of RT on tumor and supportive tissue.(35)”
ResultCartwright, I. M., Su, C., Haskins, J. S., Salinas, V. A., Sunada, S., Yu, H., Uesaka, M., Hirakawa, H., Chen, D. J., Fujimori, A., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082228 · Cited by 23
Zhang, Q., Chen, J., Ma, M., Wang, H., & Chen, H. (2018) · Chemistry of Materials · doi:10.1021/acs.chemmater.8b02251 · Cited by 23
Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer
Tanić, M., Krivokuća, A., Cavic, M. R., Mladenović, J., Karapandžić, V. P., Beck, S., Radulovic, S. S., Šušnjar, S. V., & Jankovic, R. N. (2018) · Radiation Oncology · doi:10.1186/s13014-018-1129-4 · Cited by 23
In situ vaccination caused by diverse irradiation-driven cell death programs
Wang, Y., Li, Y., Yang, Y., Swift, M. L., Zhang, Z., Wu, S., Sun, Y., & Yang, K. (2024) · Theranostics · doi:10.7150/thno.86004 · Cited by 25
“From this perspective, irradiation induces a remodeling of the tumor microenvironment through inflammatory cytokines, vascular changes and immunological components, collectively facilitating systemic anti-tumor responses [180, 181].”
BackgroundBacterial carrier-mediated drug delivery systems: a promising strategy in cancer therapy
Yan, S., Gan, Y., Xu, H., & Piao, H. (2025) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1526612 · Cited by 22
“Many experimental studies have shown that hypoxic cells are more resistant to ionizing radiation thannormoxic cells, and therefore hypoxic and necrotic areas of tumors often lead to poor therapeutic outcomes or even treatment failure (Barker et al., 2015).”
Recent Progress in Radiosensitive Nanomaterials for Radiotherapy-Triggered Drug Release
Jiang, R., Fang, Q., Liu, W., Chen, L., & Yang, H. (2025) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c23023 · Cited by 22
Tumor Microenvironment Dynamics of Triple-Negative Breast Cancer Under Radiation Therapy
Niture, S. K., Ghosh, S., Jaboin, J. J., & Seneviratne, D. S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062795 · Cited by 28
“As in other TME, RT dose and treatment regimen also can potentiate radiation resistance in the bone niche TME [157], and CAFs, and mesenchymal stem cells, can contribute to radioresistance by producing growth factors and ECM components that protect tumor cells [158].”
Cohen, G., Chandran, P., Lorsung, R. M., Tomlinson, L. E., Sundby, M., Burks, S. R., & Frank, J. A. (2020) · Cancers · doi:10.3390/cancers12020350 · Cited by 23
“B16 tumors (Figure 1A) showed a significantly decreased expression (p 0.05 one-way analysis of variance (ANOVA)) of IL1α, IL1β, IL6, IL17, macrophage colony stimulating factor (M-CSF), granulocyte CSF (G-CSF), keratinocyte chemoattractant (KC), Eotaxin, tumor necrosis factor α (TNFα), Lipopolysaccharide binding protei…”
BackgroundInfluentialDonini, M., Buti, S., Massari, F., Mollica, V., Rizzo, A., Montironi, R., Bersanelli, M., & Santoni, M. (2020) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2020.1770601 · Cited by 21
“regulatory T cells or interleukin-10 [63,64].”
Peng, L., Wang, Y., Fei, S., Wei, C., Tong, F., Wu, G., Ma, H., & Dong, X. (2020) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-500 · Cited by 22
“TAMs are absorbed into the tumor mass following RT with their main treatment-resistant contribution being characterized by the stimulation of angiogenesis and a release of growth factors (8) which, in turn, promote metastasis and tumor relapse after irradiation.”
BackgroundSingh, B., Patwardhan, R. S., Jayakumar, S., Sharma, D., & Sandur, S. K. (2020) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2020.112080 · Cited by 22
Strell, C., Tullberg, A. S., Edelmann, R. J., Akslen, L. A., Malmström, P., Fernö, M., Holmberg, E. C., Östman, A., & Karlsson, P. (2021) · Breast Cancer Research and Treatment · doi:10.1007/s10549-021-06136-4 · Cited by 22
Dai, D., Zhou, H., Yin, L., Ye, F., Yuan, X., You, T., Zhao, X., Long, W., Wang, D., He, X., et al. (2021) · Molecular Oncology · doi:10.1002/1878-0261.13134 · Cited by 22
Russo, M., Spagnuolo, C., Moccia, S., Tedesco, I., Lauria, F., & Russo, G. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010301 · Cited by 21
“As an example, in soft-tissue sarcoma cells that, when irradiated, undergo TIS, the addition of senolytic agents, venetoclax (ABT-199) or navitoclax in combination with IR induced rapid apoptotic cell death [33].”
BackgroundInfluentialvan Luijk, I. F., Smith, S. M., Ojeda, M. C. M., Oei, A. L., Kenter, G. G., & Jordanova, E. S. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11092277 · Cited by 22
“The abovementioned events, can shift the balance toward an immunoreactive, as opposed to an immunosuppressive, microenvironment leading to the recruitment and activation of cytotoxic T cells [19,20].”
BackgroundZhang, B., Xue, R., Lyu, J., Gao, A., & Sun, C. (2022) · Journal of Materials Chemistry B · doi:10.1039/d2tb00303a · Cited by 22
Jailkhani, N., Clauser, K. R., Mak, H. H., Rickelt, S., Tian, C., Whittaker, C. A., Tanabe, K. K., Purdy, S. R., Carr, S. A., & Hynes, R. O. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-1532 · Cited by 22
“Indeed, ECM plays a role in drug resistance (17 – 19) and is frequently upregulated in response to chemo and radiotherapy.”
Microalgae-based drug delivery systems in biomedical applications
Huang, H., Lang, Y., Wang, S., & Zhou, M. (2024) · Engineered Regeneration · doi:10.1016/j.engreg.2024.01.002 · Cited by 23
Hillman, G. G., Reich, L. A., Rothstein, S. E., Close, L. A., Fountain, M. D., Hankerd, K., Yunker, C. K., Rakowski, J., Quéméneur, É., & Slos, P. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0204-3 · Cited by 22
Grünow, J., Rong, C., Hischmann, J., Zaoui, K., Flechtenmacher, C., Weber, K., Plinkert, P. K., & Heß, J. (2017) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-017-0496-2 · Cited by 21
“intrinsic and acquired resistance remains a major obstacle and serves as a critical barrier for curative treatment of cancer patients, including HNSCC [15].”
Kim, E., Choi, J. Y., Hwang, S. J., & Bae, I. H. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.12.013 · Cited by 22
“kr INTRODUCTION Ionizing radiation (IR) is widely used as a therapeutic option for many cancer types, but surviving cancer cells often acquire resistance after radiotherapy.(1) Subsequently, the tumor microenvironment is modified, affecting multi-cellular responses, tissue remodeling, local recurrence, and distant met…”
BackgroundEffect of resveratrol on the radiosensitivity of 5‐FU in human breast cancer MCF‐7 cells
Aghamiri, S., Jafarpour, A., Zandsalimi, F., Aghemiri, M., & Shoja, M. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28836 · Cited by 23
“Nowadays, combined treatments using chemical/biological agents and radiotherapy have been engaged to either enhance tumor radiosensitivity or reduce radiation side‐effects.(2,33) Because the irradiation efficient enough to control the tumors far exceeds the tolerance of normal tissues.”
BackgroundAydin, Ö. F., Chandran, P., Lorsung, R. M., Cohen, G., Burks, S. R., & Frank, J. A. (2019) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2019.08.014 · Cited by 22
Benna, M., Guy, J., Bosacki, C., Jmour, O., Mrad, M. B., Ogorodniitchouk, O., Soltani, S., Lan, M., Daguenet, É., Méry, B., et al. (2020) · British Journal of Radiology · doi:10.1259/bjr.20190147 · Cited by 22
1α,25(OH)2D3 Radiosensitizes Cancer Cells by Activating the NADPH/ROS Pathway
Ji, M., Nie, J., Nie, X.-F., Hu, W., Pei, H., Wan, J., Wang, A., Zhou, G., Zhang, Z., Chang, L., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00945 · Cited by 22
Chemoradiotherapy and nanomedicine: Drug mechanisms and delivery systems
Molinaro, M., Skrodzki, D., & Pan, D. (2024) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1984 · Cited by 23
Nanomaterial-assisted delivery of CpG oligodeoxynucleotides for boosting cancer immunotherapy
Zhang, Z., Yu, L., Liu, W., & Huang, Y. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.09.044 · Cited by 21
Wang, C., Li, J., Jiang, X., Ma, X., Zhen, W., Tillman, L., Weichselbaum, R. R., & Lin, W. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202417027 · Cited by 24
Co-activating STING-TLR9 pathways promotes radiotherapy-induced cancer vaccination
Sun, Y., Liu, L., He, H., Cui, G., Zheng, Y., Ye, C., Qu, L., Sun, Y., Ji, J., Lammers, T., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.12.079 · Cited by 22
Zheng, L., Cai, W., Ke, Y., Hu, X., Yang, C., Zhang, R., Wu, H., Liu, D., Yu, H., & Wu, C. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02138-7 · Cited by 23
“RT can not only mediate the DNA damage in tumor cells but also directly affect the TME in which they are located [8, 12].”
Impact of radiation therapy on the immunological tumor microenvironment
Guilbaud, E., Naulin, F., Meziani, L., Deutsch, É., & Galluzzi, L. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.04.001 · Cited by 25
Cohen, G., Chandran, P., Lorsung, R. M., Aydin, Ö. F., Tomlinson, L. E., Rosenblatt, R. B., Burks, S. R., & Frank, J. A. (2021) · Cancers · doi:10.3390/cancers13071546 · Cited by 22
“Hot TIME also express tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), IFNγ-induced protein10 (IP-10/CXCL10), interleukin (IL) 1α, IL1β, IL2, and IL17, and endothelial CAM [8].”
BackgroundHypoxia-targeted cupric-tirapazamine liposomes potentiate radiotherapy in prostate cancer spheroids
Silva, V. L., Ruiz, A., Ali, A., Pereira, S. G. T., Seitsonen, J. J. T., Ruokolainen, J., Furlong, F. M., Coulter, J. A., & Al-Jamal, W. T. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.121018 · Cited by 21
“Hypoxia is also considered a side effect of some cancer treatments, such as photodynamic therapy, antiangiogenic therapy, radiotherapy, and androgen deprivation therapy [6], [7], contributing to therapy resistance by inducing cell quiescence [8].”
BackgroundLombardi, D., Tomasoni, M., Lorini, L., Gurizzan, C., Tomasini, D., Ardighieri, L., Battocchio, S., Bozzola, A. M., Mattavelli, D., Paderno, A., et al. (2022) · Oral Oncology · doi:10.1016/j.oraloncology.2022.105764 · Cited by 21
Orlova, A., Pavlova, K. G., Kurnikov, A. A., Maslennikova, A., Myagcheva, M., Zakharov, E., Skamnitsky, D. V., Perekatova, V., Khilov, A. V., Kovalchuk, A. V., et al. (2022) · Neoplasia · doi:10.1016/j.neo.2022.100778 · Cited by 21
Formulation of simvastatin within high density lipoprotein enables potent tumour radiosensitisation.
Dehghankelishadi, P., Maritz, M., Dmochowska, N., Badiee, P., Cheah, E., Kempson, I., Berbeco, R., & Thierry, B. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.04.017 · Cited by 18
Hydrogels for Antitumor and Antibacterial Therapy
Fang, X., Wang, C., Zhou, S., Cui, P., Hu, H., Ni, X., Jiang, P., & Wang, J. (2022) · Gels · doi:10.3390/gels8050315 · Cited by 21
“Radiation resistance is one of the reasons for the limited efficacy of RT and is related to the tumor microenvironment, such as rapid value-added and hypoxic environment [40].”
BackgroundMahmoud, A. S., Casciati, A., Bakar, Z. A., Hamzah, H. B., Ahmad, T. A. T., & Noor, M. H. M. (2023) · Genome Integrity · doi:10.14293/genint.14.1.001 · Cited by 21
“[19] The stem cell model of cancer development can explain genetic, functional, and phenotypic differences, such as increased resistance to therapy including radiotherapy.”
BackgroundMohammad, S. A., Hak, A., Pogu, S. V., & Rengan, A. K. (2023) · Cancer Innovation · doi:10.1002/cai2.53 · Cited by 20
“The immune ‐ suppressive mechanism of tumor cells is depicted in Figures 2 and 3 Other regulatory mechanisms that will retard the T ‐ cell activation include PD1 and PDL1, leading to T ‐ cell exhaustion; CTLA4 and OX 40 act as immune check-points [77].”
BackgroundHang, Y., Liu, Y., Teng, Z., Cao, X., & Zhu, H. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-01841-2 · Cited by 22
“CAFs secreted collagen fibers that increase the viscosity of the ECM and impede immune cell infiltration, which ultimately results in T-cell depletion and tumor immune tolerance [28].”
BackgroundGastric Cancer Vascularization and the Contribution of Reactive Oxygen Species
Biagioni, A., Peri, S., Versienti, G., Fiorillo, C., Becatti, M., Magnelli, L., & Papucci, L. (2023) · Biomolecules · doi:10.3390/biom13060886 · Cited by 21
Fakhri, S., Moradi, S. Z., Faraji, F., Farhadi, T., Hesami, O., Iranpanah, A., Webber, K. J., & Bishayee, A. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10119-w · Cited by 24
Vokes, E. E., Mornex, F., Sezer, A., Cheng, Y., Fang, J., Baz, D. V., Çil, T., Adjei, A. A., Ahn, M., Barlési, F., et al. (2023) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2023.09.1452 · Cited by 21
Chang, H., Wei, J.-W., Tao, Y., Ding, P., Xia, Y., Gao, Y., & Xiao, W. (2017) · Cancer Research and Treatment · doi:10.4143/crt.2017.538 · Cited by 21
Piotrowski, I., Kulcenty, K. I., Murawa, D., & Suchorska, W. M. (2018) · Medical Oncology · doi:10.1007/s12032-018-1243-z · Cited by 21
Lindegren, A., Schultz, I., Sinha, I., Cheung, L. K., Khan, A., Tekle, M., Wickman, M., & Halle, M. (2019) · British journal of surgery · doi:10.1002/bjs.11072 · Cited by 21
Self-citationRadiation Response in the Tumour Microenvironment: Predictive Biomarkers and Future Perspectives
Byrne, N. M., Tambe, P., & Coulter, J. A. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11010053 · Cited by 21
“RT is the treatment of choice for a number of cancer, designed to target and kill tumour cells; however, it triggers a myriad of effects on other components of the TME, including the vasculature, stroma and the immune compartment [5].”
BackgroundInfluentialStereotactic Body Radiotherapy Immunological Planning—A Review With a Proposed Theoretical Model
Swamy, K. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.729250 · Cited by 21
Treating Deep-Seated Tumors with Radiodynamic Therapy: Progress and Perspectives
Han, R. Q., Zhu, S., & Lin, S. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16091135 · Cited by 21
“The Hf-based nMOFs and nMOLs are also proven to amplify the RT effect by producing hydroxyl radicals [7,26].”
BackgroundHarnessing nucleotide metabolism and immunity in cancer: a tumour microenvironment perspective
Suleiman, H., Emerson, A. J., Wilson, P. M., Mulligan, K., Ladner, R. D., & LaBonte, M. J. (2024) · FEBS Journal · doi:10.1111/febs.17278 · Cited by 23
“Methods include promoting immunogenic cell death (ICD) for T-cell priming [46] via oncolytic viruses [47], radiotherapy [48], chemotherapy [49], and toll-like receptor (TLR) agonists treatments [49], alongside T-cell expansion through cancer vaccines [50].”
Chakrabarty, N., Mahajan, A., Agrawal, A., Prabhash, K., & Dcruz, A. K. (2024) · British Journal of Radiology · doi:10.1093/bjr/tqae207 · Cited by 20
Radiation Therapy Reduced Blood Levels of LDH, HIF-1α, and miR-210 in OSCC
de Souza, M. G., de Jesus, S. F., Santos, E. M., Gomes, E. S. B., Filho, A. D. P. S., Santos, E. M. S., da Silveira, L. H., Santos, S. H. S., de Paula, A. M. B., Farias, L. C., et al. (2018) · Pathology & Oncology Research · doi:10.1007/s12253-018-0517-2 · Cited by 20
“There is a healthy relationship between poor prognosis and low oxygenation levels in neoplasias [3, 9].”
BackgroundMouawad, M., Biernaski, H., Brackstone, M., Lock, M. I., Yaremko, B., Shmuilovich, O., Kornecki, A., Nachum, I. B., Muscedere, G., Lynn, K. S., et al. (2019) · Clinical and Translational Radiation Oncology · doi:10.1016/j.ctro.2019.12.004 · Cited by 20
Radiotherapy enhances uptake and efficacy of 90Y-cetuximab: A preclinical trial
Dietrich, A., Andreeff, M., Koi, L., Bergmann, R., Schubert, M., Schreiner, L., Löck, S., Sihver, W., Freudenberg, R., Hering, S., et al. (2020) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2020.11.013 · Cited by 20
Shin, S.-W., Yang, K., Lee, M., Moon, J., Son, A.-R., Kim, Y., Choi, S., Kim, D.-H., Choi, C., Lee, N., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052637 · Cited by 20
Cheng, Y., Li, W., Gui, R., Wang, C., Song, J., Wang, Z., Wang, X., Shen, Y., Wang, Z., & Hao, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.671247 · Cited by 22
“Moreover, the acquired resistance of sensitive tissues to radiotherapy is also common (Barker et al., 2015; Kim et al., 2015).”
BackgroundMultifunctional biomaterials that modulate oxygen levels in the tumor microenvironment
Hu, J., Guan, Z., & Chen, J. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.08.019 · Cited by 20
Ji, H., & Zhou, Z. (2022) · Cancers · doi:10.3390/cancers14143505 · Cited by 20
“HDRT recruits immuno-suppressive cell populations such as Tregs, myeloid-derived suppressor cells (MDSCs), and tumorassociated macrophages (TAMs) [29].”
BackgroundWong, W.-K., Liberal, F. D. C. G., & McMahon, S. J. (2022) · Cancers · doi:10.3390/cancers14153794 · Cited by 20
“To address this, further in vivo studies should be performed to account for the tumor microenvironment and its influence on radiosensitivity [36].”
BackgroundChen, M., Dong, C., & Shi, S. (2022) · ACS Materials Letters · doi:10.1021/acsmaterialslett.2c00689 · Cited by 20
Elastin-like Recombinamer Hydrogels as Platforms for Breast Cancer Modeling
Blanco‐Fernandez, B., Ibáñez‐Fonseca, A., Orbanić, D., Ximenes-Carballo, C., Pérez‐Amodio, S., Rodríguez‐Cabello, J. C., & Engel, E. (2023) · Biomacromolecules · doi:10.1021/acs.biomac.2c01080 · Cited by 22
Zhao, F., Huang, W., He, L., Nie, S., Sun, Z., Chen, T., Yin, H., & Zhao, J. (2023) · Nano Today · doi:10.1016/j.nantod.2023.101819 · Cited by 20
Huang, N.-H., Qian, A., Zou, Y., Lin, M., Pan, W., Chen, M., Meng, W., Zhang, W., & Chen, J.-X. (2023) · Theranostics · doi:10.7150/thno.84500 · Cited by 20
“Notably, the higher expression of HIF-1α was observed after treatment with RT, probably because X-ray exacerbate tumor hypoxia [10, 41, 42].”
BackgroundYu, J., Zhu, F., Yang, Y., Zhang, P., Zheng, Y., Chen, H., & Gao, Y. (2023) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2023.113606 · Cited by 20
Khan, A., Paget, J. T.-E. H., McLaughlin, M., Kyula, J., Wilkinson, M., Pencavel, T. D., Mansfield, D., Roulstone, V., Seth, R., Halle, M., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aar2041 · Cited by 20
“Fibrosis in LAEs may represent a compensatory response to tissue hypoxia caused by vascular damage (16).”
BackgroundSelf-citationWnt Signaling: Paths for Cancer Progression
Carreira-Barbosa, F., & Nunes, S. C. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-34025-4_10 · Cited by 20
Li, K., Li, M., Luo, Z. Y., Mao, Y., Yu, Y., He, Y., Zhou, J., Fei, Y., Pei, Y., & Cai, K. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.03.010 · Cited by 20
Synergy of hypoxia relief and chromatin remodeling to overcome tumor radiation resistance
Zhang, Z., Wang, L., Ding, Y., Wu, J., Hu, Y., & Yuan, A. (2020) · Biomaterials Science · doi:10.1039/d0bm00119h · Cited by 20
Woo, Y., Lee, H.-J., Kim, J., Kang, S. G., Moon, S., Han, J. A., Jung, Y. M., & Jung, Y.-J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.665420 · Cited by 21
Kadhim, M. A., Cagatay, S. T., & Elbakrawy, E. M. (2021) · International Journal of Radiation Biology · doi:10.1080/09553002.2021.1980630 · Cited by 22
“These are commonly referred to as abscopal effects (Barker et al. 2015).”
BackgroundIrradiation conditioning of adjuvanted, autologous cancer cell membrane nanoparticle vaccines
Tuo, Z., He, Q., Zhang, Z., Wang, Y., Sun, J., Wei, Q., Hu, Y., Lovell, J. F., Jin, H., & Yang, K. (2021) · Chemical Engineering Journal · doi:10.1016/j.cej.2021.134437 · Cited by 20
Miki, S., Imamichi, S., Fujimori, H., Tomiyama, A., Fujimoto, K., Satomi, K., Matsushita, Y., Matsuzaki, S., Takahashi, M., Ishikawa, E., et al. (2018) · Cancer Science · doi:10.1111/cas.13637 · Cited by 20
“It is widely known that abnormal angiogenesis occurs after tumor irradiation and that it may contribute to tumor recurrence.(36,37) Since the suppressive effect of eribulin on vascular remodeling was recently reported,(19,20) we determined whether eribulin administration neutralized the radiation-induced abnormal vasc…”
BackgroundInfluentialSpatially fractionated GRID radiation potentiates immune-mediated tumor control
Bekker, R. A., Obertopp, N., Redler, G., Peñagarícano, J., Caudell, J. J., Yamoah, K., Pilon‐Thomas, S., Moros, E. G., & Enderling, H. (2024) · Radiation Oncology · doi:10.1186/s13014-024-02514-6 · Cited by 19
Systemic tumor regression with synergy therapy: radiotherapy and CAR-T
Ma, X., Zhang, W., Zeng, M., Asavasupreechar, T., Kang, S., Li, Y., & Yu, L. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02245-3 · Cited by 19
Enhancing radiotherapy techniques for Triple-Negative breast cancer treatment
Sarlak, S., Pagès, G., & Luciano, F. (2025) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2025.102939 · Cited by 19
“Endothelial cell death and senescence contribute to long-term vascular dysfunction and release cytokines that trigger anti-tumor responses [30,54,55].”
InfluentialWang, M., Zhao, Y., Xu, K., Liu, C., Zhong, H., Wu, Y., Zhang, K., & Wei, S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1617968 · Cited by 23
“CAFs orchestrate this process through chemokine-mediated recruitment and functional reprogramming of these cell populations (75).”
Donlon, N. E., Sheppard, A., Davern, M., O’Connell, F., Phelan, J. J., Power, R. F., Nugent, T., Dinneen, K., Aird, J. J., Greene, J. P., et al. (2020) · Cancers · doi:10.3390/cancers12113356 · Cited by 18
“Chemotherapy and radiotherapy can have profound effects on reshaping the tumor microenvironment and immune response to cancer, leading to either an enhancement or suppression of anti-tumor immune responses [21,50], which depend on a myriad of tumor–host interactions.”
BackgroundEpigenetic Reprogramming of Tumor-Associated Fibroblasts in Lung Cancer: Therapeutic Opportunities
Alcaraz, J., Ikemori, R., Llorente, A., Díaz‐Valdivia, N., Reguart, N., & Vizoso, M. (2021) · Cancers · doi:10.3390/cancers13153782 · Cited by 21
“Finally, our results support that nintedanib (and possibly other antifibrotic drugs) may be particularly useful in overcoming radiotherapy-induced fibrosis in ADC, which has been pointed to as a major process underling pulmonary toxicity and ultimately resistance to radiotherapy [104].”
ResultSong, J., Zhang, S., Sun, Y., Gu, J., Ye, Z., Sun, X., & Tang, Q. (2021) · Journal of Oncology · doi:10.1155/2021/4338838 · Cited by 19
“Immune microenvironment has been proved to be closely bound up with the regulation of tumor progression and radioresistance [18, 19].”
BackgroundAlvi, S. B., Rajalakshmi, P. S., Begum, N., Jogdand, A. B., Veeresh, B., & Rengan, A. K. (2021) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.1c17054 · Cited by 20
Ni, K., Zhan, Y., Liu, Z., Zhao, X., Wang, W. “., Wang, G., Zhang, Z., Li, G., Zhang, X., & Zhang, C. (2021) · Journal of Surgical Oncology · doi:10.1002/jso.26771 · Cited by 19
Recent advances in radiosensitivity determinants in melanoma
Krayem, M., Ghanem, G. E., & Gestel, D. V. (2022) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000818 · Cited by 18
“Several vascular, stromal and immunological changes that are induced in the tumor microenvironment by irradiation may promote radioresistance and tumor recurrence [35].”
BackgroundMacrophage-Associated Disorders: Pathophysiology, Treatment Challenges, and Possible Solutions
Yadav, D. K., Pradhan, M., Singh, D., & Singh, M. R. (2022) · Springer eBooks · doi:10.1007/978-3-030-84164-5_4 · Cited by 20
Lip, H., Amini, M. A., Zetrini, A., Cai, P., Abbasi, A. Z., Bristow, R. G., Rauth, A. M., & Wu, X. Y. (2022) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2022.02.026 · Cited by 19
A DNA-structured mathematical model of cell-cycle progression in cyclic hypoxia
Celora, G. L., Bader, S. B., Hammond, E. M., Maini, P. K., Pitt‐Francis, J., & Byrne, H. M. (2022) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2022.111104 · Cited by 17
Sun, H., Sun, R., Song, X., Gu, W., & Shao, Y. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03392-w · Cited by 19
“Previous studies have shown that the tumor microenvironment mediates the resistance to radiotherapy [56].”
Background
Metadata
- Authors
- Barker, H. E., Paget, J. T. E., Khan, A. A., & Harrington, K. J.
- Affiliations
- Institute of Cancer Research (GB)
- Corresponding author
- Barker, Holly E.
- Venue
- Nature Reviews Cancer
- Published
- 2015-06-24
- Volume
- 15
- Issue
- 7
- Pages
- 409-425
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC4896389
- OpenAlex
- W1912124796
- Cited by
- 2,144
- References
- 200
- Citations by year
- 2026: 181 · 2025: 215 · 2024: 246 · 2023: 242 · 2022: 249 · 2021: 256 · 2020: 230 · 2019: 175 · 2018: 161 · 2017: 119 · 2016: 63 · 2015: 7
- FWCI
- 12.40
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-07-24)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research UK (C46 ⁄ A10588, C7224/A13407, A13407, 13407)
- National Institute for Health and Care Research (CL-2014-22-003)
- Rosetrees Trust
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- tumor microenvironment, radioresistance (biology), radiotherapy, tumor stroma, tumor recurrence, vascular changes, immunological changes, combination therapy, molecularly targeted agents
- MeSH terms
- Animals, Fibroblasts, Humans, Immune Tolerance, Neoplasm Recurrence, Local, Neoplasms, Radiation Tolerance, Cell Hypoxia, Transforming Growth Factor beta, Vascular Endothelial Growth Factor A, Tumor Microenvironment
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