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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
Cited by
Sorted by citations
Items 201–300 of 1,005
The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer
Parida, S., & Sharma, D. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.04.001 · Cited by 126
Biomarker-driven molecular imaging probes in radiotherapy
Li, H., Gong, Q., & Luo, K. (2024) · Theranostics · doi:10.7150/thno.97768 · Cited by 117
“To note, biomarkers associated with radiotherapy for indicating biological changes in molecules/proteins, intracellular organelles, cells, and tissues/organs, will be explored and discussed in this review [20].”
BackgroundOvercoming cold tumors: a combination strategy of immune checkpoint inhibitors
Ouyang, P., Wang, L., Wu, J., Tian, Y., Chen, C., Li, D., Yao, Z., Chen, R., Xiang, G., Gong, J., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1344272 · Cited by 123
Harada, H. (2016) · Journal of Radiation Research · doi:10.1093/jrr/rrw012 · Cited by 116
“HIF-1-MEDIATED RADIORESISTANCE OF CANCER CELLS Recent advances in molecular biological research in the fields of radiation oncology and biology have led to the potential of HIF-1 in enhancing the radioresistance of cancer cells being recognized [5, 7, 35].”
BackgroundJiang, J. W., Shen, N., Ci, T., Tang, Z., Gu, Z., Li, G., & Chen, X. (2019) · Advanced Materials · doi:10.1002/adma.201904278 · Cited by 114
Sissy, C. E., Kirilovsky, A., den Eynde, M. V., Mușină, A.-M., Aniței, M.-G., Romero, A., Marliot, F., Junca, A., Doyen, J., Mlecnik, B., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-0337 · Cited by 113
“the presence of a suppressive microenvironment (30).”
Naz, S., Sowers, A. L., Choudhuri, R., Wissler, M. F., Gamson, J., Mathias, A., Cook, J. A., & Mitchell, J. B. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3575 · Cited by 113
“These findings are crucial for radiotherapy because both enhanced tumor hypoxia (induction of HIF-1) and mTOR activation are well-documented mechanisms for altering radiosensitivity in tumors (24, 50).”
BackgroundMultifunctional Bi2WO6 Nanoparticles for CT-Guided Photothermal and Oxygen-free Photodynamic Therapy
Zhang, C., Ren, J., Hua, J., Xia, L., He, J., Huo, D., & Hu, Y. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b16000 · Cited by 112
Krisnawan, V. E., Stanley, J. A., Schwarz, J. K., & DeNardo, D. G. (2020) · Cancers · doi:10.3390/cancers12102916 · Cited by 115
“Radiation therapy (RT) is a powerful anti-cancer therapeutic used to treat up to 50−60% of cancer patients [12,13].”
BackgroundInfluentialThe role of N6-methyladenosine mRNA in the tumor microenvironment
Li, M., Zha, X., & Wang, S. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188522 · Cited by 114
Li, H., Wang, M., Huang, B., Zhu, S., Zhou, J., Chen, D., Cui, R., Zhang, M., & Sun, Z. (2021) · Nature Communications · doi:10.1038/s41467-021-27485-0 · Cited by 113
Zhang, R., Li, J., Zhang, T., Amini, M. A., He, C., Lu, B., Ahmed, T., Lip, H., Rauth, A. M., & Wu, X. Y. (2018) · Acta Pharmacologica Sinica · doi:10.1038/aps.2018.33 · Cited by 112
Bian, Z., Shi, L., Kidder, K., Zen, K., Garnett‐Benson, C., & Liu, Y. (2021) · Nature Communications · doi:10.1038/s41467-021-23442-z · Cited by 114
Determinants and functions of CAFs secretome during cancer progression and therapy
Linares, J., Marín-Jiménez, J. A., Badia-Ramentol, J., & Calon, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.621070 · Cited by 110
“Importantly, a vast body of evidence suggests that RT enhances paracrine signaling between fibroblasts and cancer cells through the IGF and TGF-beta pathways (Barker et al., 2015; Tommelein et al., 2018).”
BackgroundHypoxia Signaling in Cancer: From Basics to Clinical Practice
Sebestyén, A., Kopper, L., Dankó, T., & Tímár, J. (2021) · Pathology and Oncology Research · doi:10.3389/pore.2021.1609802 · Cited by 110
Jiang, W., Li, Q., Xiao, L., Dou, J., Liu, Y., Yu, W., Ma, Y., Li, X., You, Y., Tong, Z., et al. (2018) · ACS Nano · doi:10.1021/acsnano.8b01508 · Cited by 113
Meng, Z., Chao, Y., Zhou, X., Liang, C., Liu, J., Zhang, R., Cheng, L., Yang, K., Pan, W., Zhu, M., et al. (2018) · ACS Nano · doi:10.1021/acsnano.8b04544 · Cited by 112
“to the resistance or failure of brachytherapy to treat certain types of cancers.(8-10) Moreover, the”
Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas
Prezado, Y., Jouvion, G., Patriarca, A., Nauraye, C., Guardiola, C., Juchaux, M., Lamirault, C., Labiod, D., Jourdain, L., Sebrié, C., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-34796-8 · Cited by 110
Novel Metal Polyphenol Framework for MR Imaging-Guided Photothermal Therapy
Zhao, G., Wu, H., Feng, R., Wang, D., Xu, P., Jiang, P., Kang, Y., Wang, H., Guo, Z. G., & Chen, Q. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b16222 · Cited by 109
A Magneto-Optical Nanoplatform for Multimodality Imaging of Tumors in Mice
Song, G., Zheng, X., Wang, Y., Xia, X., Chu, S., & Rao, J. (2019) · ACS Nano · doi:10.1021/acsnano.9b01436 · Cited by 110
Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies
Sztiller-Sikorska, M., & Czyż, M. (2020) · Pharmaceuticals · doi:10.3390/ph13080194 · Cited by 112
“Radiotherapy is currently used to treat localized tumors such as cancers of the skin, brain, breast, and prostate, but it is delimited by side effects and late complications resulting from high-dose radiation and development of resistance [173].”
BackgroundChen, D., Barsoumian, H. B., Yang, L., Younes, A. I., Verma, V., Hu, Y., Menon, H., Wasley, M., Masropour, F., Mosaffa, S., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0744 · Cited by 107
Thomas, R. P., Nagpal, S., Iv, M., Soltys, S. G., Bertrand, S., Pelpola, J. S., Ball, R. L., Yang, J., H, V. S. M. P., Chernikova, S. B., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1421 · Cited by 106
“3) is thought to be the result of the presence of radioresistant hypoxic cells in the residual tumor after surgery as well as radiation-induced HIF-1 levels that lead to enhanced cytokine production and endothelial cell radioresistance (4).”
BackgroundThe p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer
García-Hernández, L., García‐Ortega, M. B., Ruiz-Alcalá, G., Carrillo, E., Marchal, J. A., & García, M. Á. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010370 · Cited by 111
“In addition, the stroma, which dynamically supports the TME, is formed by the extracellular matrix, a different type of cells, including fibroblasts, infiltrated immune cells, and histological structures such as the blood vessels or connective tissue [72] (Figure 3).”
BackgroundKosinsky, Y., Dovedi, S. J., Peskov, K. V., Voronova, V., Chu, L., Tomkinson, H. K., Al-Huniti, N. H., Stanski, D. R., & Helmlinger, G. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0327-9 · Cited by 105
“For example, high single RT doses (8–16 Gy) are known to induce endothelial cell apoptosis, which may lead to changes in tumor vasculature [35].”
BackgroundGuipaud, O., Jaillet, C., Clément-Colmou, K., François, A., Supiot, S., & Milliat, F. (2018) · British Journal of Radiology · doi:10.1259/bjr.20170762 · Cited by 110
Platinum(IV) complex-based two-in-one polyprodrug for a combinatorial chemo-photodynamic therapy
Guo, D., Xu, S., Huang, Y., Jiang, H., Yasen, W., Wang, N., Su, Y., Qian, J., Li, J., Zhang, C., et al. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.05.052 · Cited by 105
Huang, W., Zhang, L., Yang, M. Y., Wu, X., Wang, X., Huang, W., Lu, Y., Pan, H., Wang, Y., Wang, Z., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01878-x · Cited by 105
Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs” of Radiotherapy
Rakotomalala, A., Escande, A., Furlan, A., Meignan, S., & Lartigau, E. F. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.742215 · Cited by 118
Dhaliwal, A. K., & Zheng, G. (2019) · Theranostics · doi:10.7150/thno.37204 · Cited by 107
“Reductions in pressure are due to a combination of factors, including vascular regression, death of tumor cells which compress microvasculature, and decreased resistance to blood flow [56,57].”
BackgroundWhitson, R. J., Lee, A. G., Urman, N. M., Mirza, A., Yao, C., Brown, A. S., Li, J., Shankar, G., Fry, M. A., Atwood, S. X., et al. (2018) · Nature Medicine · doi:10.1038/nm.4476 · Cited by 102
Li, D., Sedano, S., Allen, R. S., Gong, J., Cho, M. T., & Sharma, S. (2019) · Cancers · doi:10.3390/cancers11060841 · Cited by 103
“Radiation has been found to enhance the antitumoral immune response of immune checkpoint inhibitors and is considered an inducer of immunogenic cell death leading to improved immunogenicity [80].”
BackgroundLiu, N., Zhu, J., Zhu, W., Chen, L., Li, M., Shen, J., Chen, M., Wu, Y., Pan, F., Deng, Z., et al. (2023) · Advanced Materials · doi:10.1002/adma.202302220 · Cited by 103
Liu, Y., Zhou, J., Li, Q., Li, L., Jia, Y., Geng, F., Zhou, J., & Yin, T. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.02.019 · Cited by 103
Advances in Biomimetic Nanoparticles for Targeted Cancer Therapy and Diagnosis
Beh, C. Y., Prajnamitra, R. P., Chen, L.-L., & Hsieh, P. C. H. (2021) · Molecules · doi:10.3390/molecules26165052 · Cited by 109
“The absence of oxygen in hypoxia prevents DNA breakage and promotes DNA repair, ultimately making the tumour resistant to radiotherapy [77].”
BackgroundXu, H., Cao, C., Ren, Y., Weng, S., Liu, L., Guo, C., Wang, L., Han, X., Ren, J., & Liu, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.949490 · Cited by 110
Gou, S., Liu, W., Wang, S., Chen, G., Chen, Z., Qiu, L., Zhou, X., Wu, Y., Qi, Y., & Gao, Y. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c03243 · Cited by 107
Development and characterisation of acquired radioresistant breast cancer cell lines
Gray, M., Turnbull, A., Ward, C., Meehan, J., Martínez-Pérez, C., Bonello, M., Pang, L. Y., Langdon, S. P., Kunkler, I. H., Murray, A., et al. (2019) · Radiation Oncology · doi:10.1186/s13014-019-1268-2 · Cited by 103
Jin, J., & Zhao, Q. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-020-00629-y · Cited by 103
Huang, W., He, L., Ouyang, J., Chen, Q., Chuang, L. I. U., Tao, W., & Chen, T. (2020) · Matter · doi:10.1016/j.matt.2020.08.027 · Cited by 100
Patel, R. R., He, K., Barsoumian, H. B., Chang, J. Y., Tang, C. Z., Verma, V., Comeaux, N. I., Chun, S. G., Gandhi, S. J., Truong, M. T., et al. (2021) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2021.06.037 · Cited by 105
Radiation‐Induced Immunogenic Cell Death for Cancer Radioimmunotherapy
Liu, T., Pei, P., Shen, W., Hu, L. T., & Yang, K. (2023) · Small Methods · doi:10.1002/smtd.202201401 · Cited by 104
Lipid Metabolism and Cancer Immunotherapy: Immunosuppressive Myeloid Cells at the Crossroad
Bleve, A., Durante, B., Sica, A., & Consonni, F. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165845 · Cited by 101
“In this scenario, cancer immunotherapy has emerged as a revolutionary therapeutic approach, aiming at improving anti-tumor immune responses with fewer off-target effects than chemo- and radiotherapy [15,72].”
BackgroundYuan, D., Xu, J., Wang, J., Pan, Y., Fu, J., Bai, Y., Zhang, J., & Shao, C. (2016) · Oncotarget · doi:10.18632/oncotarget.9017 · Cited by 86
“It has been reported that lung cancer could effectively evade radiation-mediated cell killing by a number of strategies including radioresistance and tumor microenvironment mediated signaling [1, 2].”
BackgroundMetformin Suppresses Tumor Progression by Inactivating Stromal Fibroblasts in Ovarian Cancer
Xu, S., Yang, Z., Jin, P., Yang, X., Li, X., Xiao, W., Wang, Y., Long, S., Zhang, T., Chen, G., et al. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0927 · Cited by 100
“When tumors suffer from stress such as radiotherapy and chemotherapy, CAFs inside can be transformed into a stronger proinflammatory phenotype and the inflammation cascade can be triggered more intensely (10, 11).”
BackgroundLycopene exerts anti-inflammatory effect to inhibit prostate cancer progression
Li, B., Jiang, L.-N., & Liu, Y.-B. (2018) · Asian Journal of Andrology · doi:10.4103/aja.aja_70_18 · Cited by 97
Liu, C., Mann, D., Sinha, U. K., & Kokot, N. (2018) · Journal of Otolaryngology - Head and Neck Surgery · doi:10.1186/s40463-018-0302-y · Cited by 97
“Hypoxia-inducible factor 1α (HIF1α) is stabilized under hypoxic conditions, which leads to the upregulation of genes involved in cell survival [44].”
BackgroundTian, L., Wang, Y., Sun, L., Xu, J., Chao, Y., Yang, K., Wang, S., & Liu, Z. (2019) · Matter · doi:10.1016/j.matt.2019.07.007 · Cited by 97
Fan, Y., Tu, W., Shen, M., Chen, X., Ning, Y., Li, J., Chen, T., Wang, H., Yin, F.-F., Liu, Y., et al. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909285 · Cited by 97
Early stratification of radiotherapy response by activatable inflammation magnetic resonance imaging
Zhou, Z., Deng, H., Yang, W., Wang, Z., Lin, L., Munasinghe, J., Jacobson, O., Liu, Y., Tang, L., Ni, Q., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16771-y · Cited by 96
Chitosan/γ-PGA nanoparticles-based immunotherapy as adjuvant to radiotherapy in breast cancer
Castro, F., Pinto, M. L., Pereira, C. L., Serre, K., Barbosa, M. A., Vermaelen, K. Y., Gärtner, F., Gonçalves, R. M., Wever, O. D., & Oliveira, M. J. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120218 · Cited by 96
“Accordingly, the accumulation of myeloid cells, including MDSCs and TAMs, has been associated with tumor progression and metastasis [7 – 10].”
Biological Adaptations of Tumor Cells to Radiation Therapy
Carlos‐Reyes, Á., Muñiz-Lino, M. A., Romero‐Garcia, S., López‐Camarillo, C., & la Cruz, O. N. H.-D. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.718636 · Cited by 106
“However, an increased tumor volume, low oxygen tension, and dysregulation of key genes can lead to tolerance and clonal selection of tumor cells to radiation, thus reducing sensitivity to radiotherapy, leading to tumor recurrence and therapy resistance (2, 5, 6).”
BackgroundTitanium carbide nanosheets with defect structure for photothermal-enhanced sonodynamic therapy
Li, G., Zhong, X., Wang, X., Gong, F., Lei, H., Zhou, Y., Li, C., Xiao, Z., Ren, G., Zhang, L., et al. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.06.021 · Cited by 151
Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway
Wang, Y., Zhao, M., He, S., Luo, Y., Zhao, Y., Cheng, J. Q., Gong, Y., Xie, J., Wang, Y., Hu, B., et al. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1423-5 · Cited by 100
Crossed Pathways for Radiation-Induced and Immunotherapy-Related Lung Injury
Zhang, Z., Zhou, J., Verma, V., Liu, X., Wu, M., Yu, J., & Chen, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.774807 · Cited by 97
Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment
Pan, Y., Liu, L., Mou, X., & Cai, Y. (2023) · ACS Nano · doi:10.1021/acsnano.3c07763 · Cited by 98
Qin, Q., Yu, R., Eriksson, J., Tsai, H., & Zhu, H. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216859 · Cited by 102
Nanoprobe-based molecular imaging for tumor stratification
Ma, X., Mao, M., He, J., Liang, C., & Xie, H. (2023) · Chemical Society Reviews · doi:10.1039/d3cs00063j · Cited by 96
Gupta, K., & Burns, T. C. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00503 · Cited by 100
“Many radiation-induced changes in the TME have been documented (115, 116).”
BackgroundLiu, L., Zhang, Z., Zhou, L., Hu, L., Yin, C., Qing, D., Huang, S., Cai, X., & Chen, Y. (2020) · Experimental Cell Research · doi:10.1016/j.yexcr.2020.111956 · Cited by 94
Bao, Z., Wang, Y., Wang, Q., Fang, S., Shan, X., Wang, J., & Jiang, T. (2021) · Frontiers of Medicine · doi:10.1007/s11684-020-0760-2 · Cited by 93
Cancer-Associated Fibroblasts in the Hypoxic Tumor Microenvironment
Kim, I., Choi, S., Yoo, S., Lee, M., & Kim, I. (2022) · Cancers · doi:10.3390/cancers14143321 · Cited by 107
“Radiotherapy induces spatial and temporal fluctuations in oxygen concentrations, which potentiates the fibrotic and pro-angiogenic responses and immune modulation within the tumor microenvironment [76,77].”
BackgroundLiu, C., Wang, X., Qin, W., Tu, J., Li, C., Zhao, W., Ma, L., Liu, B., Qiu, H., & Yuan, X. (2023) · 癌症：英文版 · doi:10.1002/cac2.12412 · Cited by 99
“As a universal standard of care for many cancer types, radiotherapy plays a complex role in altering the tumor microenvironment [12].”
BackgroundXu, H., Wang, T., Yang, C., Li, X., Liu, G., Yang, Z., Singh, P. K., Krishnan, S., & Ding, D. (2018) · Advanced Functional Materials · doi:10.1002/adfm.201707140 · Cited by 93
Ju, C., Wen, Y., Zhang, L., Wang, Q., Xue, L., Shen, J., & Zhang, C. (2018) · Small · doi:10.1002/smll.201804191 · Cited by 93
Zhuang, J., Ma, Z., Li, N., Chen, H., Yang, L., Lü, Y., Guo, K., Zhao, N., & Tang, B. Z. (2023) · Advanced Materials · doi:10.1002/adma.202309488 · Cited by 92
Marciscano, A. E. E., Haimovitz‐Friedman, A., Lee, P. P., Tran, P. T., Tomé, W. A., Guha, C., Kong, F., Sahgal, A., Naqa, I. E., Rimner, A., et al. (2019) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2019.02.046 · Cited by 96
Xu, Q., Zhang, H., Liu, H., Han, Y., Qiu, W., & Li, Z. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121287 · Cited by 91
Zhang, Y., Feng, Z., Liu, J., Li, H., Su, Q., Zhang, J., Huang, P., Wang, W., & Liu, J. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.12.033 · Cited by 90
Delivering metal ions by nanomaterials: Turning metal ions into drug-like cancer theranostic agents
Liu, C., Guo, L., Wang, Y., Zhang, J., & Fu, C. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215332 · Cited by 90
Xu, Z., Zhen, W., McCleary, C., Luo, T., Jiang, X., Peng, C. Y., Weichselbaum, R. R., & Lin, W. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c04602 · Cited by 88
Tumour and microenvironment crosstalk in NSCLC progression and response to therapy
Rahal, Z., Darzi, R. E., Moghaddam, S. J., Cascone, T., & Kadara, H. N. (2025) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-025-01021-1 · Cited by 105
“By contrast, radiotherapy alone or with chemotherapy can perpetuate immunosuppressive TME states through recruitment of myeloid cells or hypoxia, which could limit the efficacy of ICIs if treatment timing or dosing fails to align with immune priming 176,177 .”
Melatonin as an anti-inflammatory agent in radiotherapy
Najafi, M., Shirazi, A., Motevaseli, E., Rezaeyan, A., Salajegheh, A., & Rezapoor, S. (2017) · Inflammopharmacology · doi:10.1007/s10787-017-0332-5 · Cited by 87
Mechanistic Modelling of Radiation Responses
McMahon, S. J., & Prise, K. M. (2019) · Cancers · doi:10.3390/cancers11020205 · Cited by 88
“Moreover, there is a growing interest in a range of other factors which alter radiation responses, including radiations of different qualities [22], radiationresponse modifying drugs [23], microenvironmental features of e tumor [24], and inter-patient variations in radiation sensitivity [25].”
BackgroundImmune Checkpoint Inhibitor‐Based Strategies for Synergistic Cancer Therapy
He, M., Yang, T., Wang, Y., Wang, M., Chen, X., Ding, D., Zheng, Y., & Chen, H. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202002104 · Cited by 92
Huang, Z., Yao, D., Ye, Q., Jiang, H., Gu, R., Ji, C., Wu, J., Hu, Y., & Yuan, A. (2021) · ACS Nano · doi:10.1021/acsnano.0c10764 · Cited by 88
Tissue factor is a critical regulator of radiation therapy-induced glioblastoma remodeling
Jeon, H.-M., Kim, J., Cho, H. J., Lee, W. J., Nguyen, D., Kim, S. S., Oh, Y. T., Kim, H., Jung, C., Piñero, G., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.06.007 · Cited by 91
Immune recognition of irradiated cancer cells
Wennerberg, E., Vanpouille‐Box, C., Bornstein, S., Yamazaki, T., Demaria, S., & Galluzzi, L. (2017) · Immunological Reviews · doi:10.1111/imr.12568 · Cited by 88
PL–W18O49–TPZ Nanoparticles for Simultaneous Hypoxia-Activated Chemotherapy and Photothermal Therapy
Zhao, P., Ren, S., Liu, Y., Huang, W., Zhang, C., & He, J. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b17323 · Cited by 87
Wang, Z., Chang, Z., Shao, D., Zhang, F., Chen, F., Li, L., Ge, M., Hu, R., Zheng, X., Wang, Y., et al. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b12879 · Cited by 87
Moreira, D., Sampath, S., Won, H., White, S. V., Su, Y., Alcantara, M. B., Wang, C., Lee, P. P., Maghami, E. G., Massarelli, E., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137001 · Cited by 87
“The extrinsic effects of the TME are likely influencing the outcome of RT (12, 16, 17).”
BackgroundRecent advances in immunotherapy, immunoadjuvant, and nanomaterial-based combination immunotherapy
Zhou, B., Liu, J., Lin, M., Zhu, J., & Chen, W. R. (2021) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2021.214009 · Cited by 86
Nanomedicine Combats Drug Resistance in Lung Cancer
Zheng, X., Song, X.-H., Zhu, G., Pan, D., Li, H., Hu, J., Xiao, K., Gong, Q., Gu, Z., Luo, K., et al. (2023) · Advanced Materials · doi:10.1002/adma.202308977 · Cited by 94
Biology and therapeutic targeting of tumour‐associated macrophages
Beltraminelli, T., & Palma, M. D. (2020) · The Journal of Pathology · doi:10.1002/path.5403 · Cited by 87
“Despite the broad clinical use of ionizing radiation in the inoperable or adjuvant (post-surgical) setting, the involvement of macrophages in human tumour response to radiotherapy remains unclear [204,206].”
BackgroundInfluentialDeng, X., Liang, H., Yang, W., & Shao, Z. (2020) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2020.111913 · Cited by 86
Wu, X., Luo, Q., & Liu, Z. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02760-y · Cited by 91
Paganetti, H. (2021) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2021.08.015 · Cited by 86
Dong, Z., Wang, C., Gong, Y., Zhang, Y., Fan, Q., Hao, Y., Li, Q., Wu, Y., Zhong, X., Yang, K., et al. (2022) · ACS Nano · doi:10.1021/acsnano.2c02688 · Cited by 87
Tumor Immunology and Immunotherapy of Non-Small-Cell Lung CancerPreprint
Cascone, T., Fradette, J. J., Pradhan, M., & Gibbons, D. L. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a037895 · Cited by 91
Combined Radiation Therapy and Immune Checkpoint Blockade Therapy for Breast Cancer
Hu, Z. I., Ho, A. Y., & McArthur, H. L. (2017) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2017.05.029 · Cited by 88
Liu, J., Wang, H., Yi, X., Chao, Y., Geng, Y., Xu, L., Yang, K., & Liu, Z. (2017) · Advanced Functional Materials · doi:10.1002/adfm.201703832 · Cited by 85
Dou, Y., Liu, Y., Zhao, F., Guo, Y., Li, X., Wu, M., Chang, J., & Yu, C. (2018) · Theranostics · doi:10.7150/thno.27351 · Cited by 85
“damage and cytotoxic reactive oxygen species (ROS), ionizing radiation (IR) may also alter tumor microenvironment (TME) to promote radioresistance [3-4].”
BackgroundRelationship and interactions of curcumin with radiation therapy
Verma, V. (2016) · World Journal of Clinical Oncology · doi:10.5306/wjco.v7.i3.275 · Cited by 85
Ultrahigh Dose-rate Radiotherapy: Next Steps for FLASH-RT
Harrington, K. J. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1796 · Cited by 84
Self-citationZhang, L., Shi, H. R., Chen, H., Gong, A., Liu, Y., Song, L., Xu, X., You, T., Fan, X., Wang, D., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1956-8 · Cited by 84
Emerging Technologies for Local Cancer Treatment
Chua, C. Y. X., Ho, J., Demaria, S., Mauro Ferrari, B., & Grattoni, A. (2020) · Advanced Therapeutics · doi:10.1002/adtp.202000027 · Cited by 88
Extracellular ATP and Adenosine in Cancer Pathogenesis and Treatment
Chiarella, A. M., Ryu, Y. K., Manji, G. A., & Rustgi, A. K. (2021) · Trends in cancer · doi:10.1016/j.trecan.2021.04.008 · Cited by 87
The Promise of Nanoparticles-Based Radiotherapy in Cancer Treatment
Haque, M., Shakil, M. S., & Mahmud, K. M. (2023) · Cancers · doi:10.3390/cancers15061892 · Cited by 88
“Moreover, progression of a hypoxic TME after irradiation is the one of the primary factors in RR development [184].”
BackgroundTargets for improving tumor response to radiotherapy
Mortezaee, K., Parwaie, W., Motevaseli, E., Mirtavoos‐Mahyari, H., Musa, A. E., Shabeeb, D., Esmaely, F., Najafi, M., & Farhood, B. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105847 · Cited by 82
“This is associated with higher presentation of damage-associated molecular patterns (DAMPs) to CTLs, leading to more release of anti-cancer cytokines [47].”
BackgroundKnops, A. M., South, A., Rodeck, U., Martinez-Outschoorn, U., Harshyne, L., Johnson, J., Luginbuhl, A., & Curry, J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.565306 · Cited by 76
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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