Cited by 2,144Cancer Cells and MetastasisEffects of Radiation ExposureCancer, Hypoxia, and Metabolism

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The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence

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Barker, Holly E., Paget, James T. E., Khan, Aadil A., Harrington, Kevin J.·2015·Nature Reviews Cancer

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Abstract

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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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
Retracted
MMP-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
Retracted
Hallmarks 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
The hallmarks of cancer
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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Items 501–600 of 1,005

MiR-338-5p enhances the radiosensitivity of esophageal squamous cell carcinoma by inducing apoptosis through targeting survivin
Park, M., Yoon, H.-J., Kang, M. C., Kwon, J., & Lee, H. W. (2017) · Scientific Reports · doi:10.1038/s41598-017-10977-9 · Cited by 50
The immunocytokine L19-IL2: An interplay between radiotherapy and long-lasting systemic anti-tumour immune responses
Rekers, N. H., Pimentel, V. O., Yaromina, A., Lieuwes, N. G., Biemans, R., Zegers, C. M. L., Germeraad, W. T. V., Limbergen, E. J. V., Neri, D., Dubois, L. J., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1414119 · Cited by 52
Development of a thermosensitive protein conjugated nanogel for enhanced radio-chemotherapy of cancer
Maiti, D., Chao, Y., Dong, Z., Yi, X., He, J., Liu, Z., & Yang, K. (2018) · Nanoscale · doi:10.1039/c8nr03986k · Cited by 50
The integrated high-resolution reflection-mode photoacoustic and fluorescence confocal microscopy
Liu, C., Liao, J., Chen, L., Chen, J., Ding, R., Gong, X., Cui, C., Pang, Z., Zheng, W., & Song, L. (2019) · Photoacoustics · doi:10.1016/j.pacs.2019.02.001 · Cited by 50
“, tumor blood vessel normalization [34]) of various drugs for tumor treatment [35].”
Background
Microparticles from tumors exposed to radiation promote immune evasion in part by PD-L1
Timaner, M., Kotsofruk, R., Raviv, Z., Magidey, K., Shechter, D., Kan, T., Nevelsky, A., Daniel, S., de Vries, E. G. E., Zhang, T., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0971-7 · Cited by 50
Tumor-derived extracellular vesicles: Regulators of tumor microenvironment and the enlightenment in tumor therapy
Chen, J., Fei, X., Wang, J., & Cai, Z. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105041 · Cited by 52
Association of Immunotherapy With Survival Among Patients With Brain Metastases Whose Cancer Was Managed With Definitive Surgery of the Primary Tumor
Amin, S., Baine, M. J., Meza, J. L., & Lin, C. H. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.15444 · Cited by 50
“The median (range) age at diagnosis was 61 (19-90) years.”
Background
Imaging of Tumor Hypoxia With Radionuclide-Labeled Tracers for PET
Huang, Y., Fan, J., Li, Y., Fu, S., Chen, Y., & Wu, J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.731503 · Cited by 53
Impact of the microbiome on cancer progression and response to anti-cancer therapies
Rosean, C. B., Feng, T.-Y., Azar, F. N., & Rutkowski, M. R. (2019) · Advances in cancer research · doi:10.1016/bs.acr.2019.03.005 · Cited by 52
“In mice with a replete microbiome, the enhanced intestinal permeability caused by radiation treatment results in bacterial translocation from the lumen of the intestine into draining lymph nodes, resulting in significant mucosal inflammation, toxicity, and immune activation against bacterial species (Barker et al., 20…”
Background
A platelet-mimicking theranostic platform for cancer interstitial brachytherapy
Lyu, M., Chen, M., Liu, L., Zhu, D., Wu, X., Li, Y., Rao, L., & Bao, Z. (2021) · Theranostics · doi:10.7150/thno.61259 · Cited by 49
Tumor microenvironments self-activated cascade catalytic nanoscale metal organic frameworks as ferroptosis inducer for radiosensitization
Liang, Y., Peng, C., Su, N., Li, Q., Chen, S., Wu, D., Wu, B., Gao, Y., Xu, Z., Dan, Q., et al. (2022) · Chemical Engineering Journal · doi:10.1016/j.cej.2022.135309 · Cited by 49
Therapeutic application of manganese-based nanosystems in cancer radiotherapy
Pan, S., Sun, Z., Zhao, B., Miao, L., Zhou, Q., Chen, T., & Zhu, X. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122321 · Cited by 50
Smart composite scaffold to synchronize magnetic hyperthermia and chemotherapy for efficient breast cancer therapy
Sun, R., Chen, H., Wang, M., Yoshitomi, T., Takeguchi, M., Kawazoe, N., Yang, Y., & Chen, G. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122511 · Cited by 49
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Wang, S., Cheng, M., Wang, S., Jiang, W., Yang, F., Shen, X., Zhang, L., Yan, X., Jiang, B., & Fan, K. (2024) · Advanced Materials · doi:10.1002/adma.202403921 · Cited by 49
Self‐Oxygenating PROTAC Microneedle for Spatiotemporally‐Confined Protein Degradation and Enhanced Glioblastoma Therapy
Jiang, X., Lai, Y., Xia, W., Yang, W., Wang, J., Pan, J., Zhao, Q., Zhou, X., Li, S., Zhang, S., et al. (2025) · Advanced Materials · doi:10.1002/adma.202411869 · Cited by 54
Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and recruit Foxp3+ regulatory T cells in murine colon cancer
Chen, X., Takemoto, Y., Deng, H., Middelhoff, M. A., Friedman, R. A., Chu, T. H., Churchill, M., Ma, Y., Nagar, K. K., Tailor, Y. H., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1290034 · Cited by 49
“clarify the precise contribution of the various myeloid lineages to tumor progression.(25) In the current study, we compared the role and function of the HDCC myeloid lineage to the remainder of the HDC¡ myeloid cells during carcinogenesis, using a”
Background
Hypothesis: can the abscopal effect explain the impact of adjuvant radiotherapy on breast cancer mortality?
Jatoi, I., Benson, J. R., & Kunkler, I. H. (2018) · npj Breast Cancer · doi:10.1038/s41523-018-0061-y · Cited by 53
Radiation-Induced Transformation of Immunoregulatory Networks in the Tumor Stroma
Martínez-Zubiaurre, I., Chalmers, A. J., & Hellevik, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01679 · Cited by 52
“Am J Physiol Cell Physiol (2010) 299(3):C589–605.”
BackgroundInfluential
IDO1 Inhibition Overcomes Radiation-Induced “Rebound Immune Suppression” by Reducing Numbers of IDO1-Expressing Myeloid-Derived Suppressor Cells in the Tumor Microenvironment
Li, A., Barsoumian, H. B., Schoenhals, J. E., Caetano, M. S., Wang, X., Menon, H., Valdecanas, D. R., Niknam, S., Younes, A. I. A., Cortez, M. A., et al. (2019) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2019.03.022 · Cited by 49
Oral mucosal mesenchymal stem cell‑derived exosomes: A potential therapeutic target in oral premalignant lesions
Li, W., Han, Y., Zhao, Z., Ji, X., Wang, X., Jin, J., Wang, Q., Guo, X. Y., Cheng, Z., Lu, M., et al. (2019) · International Journal of Oncology · doi:10.3892/ijo.2019.4756 · Cited by 49
“also contribute to this transformation (7,8).”
Integrating nanomedicine into clinical radiotherapy regimens
DuRoss, A. N., Neufeld, M. J., Rana, S. R., Thomas, C. R., & Sun, C. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.07.002 · Cited by 49
“Along with its effects on the immune system, radiation can influence the entire tumor microenvironment [161].”
Background
Construction of Nucleus‐Targeting Iridium Nanocrystals for Photonic Hyperthermia‐Synergized Cancer Radiotherapy
Wang, L., Zhang, T., Huo, M., Guo, J., Chen, Y., & Xu, H. (2019) · Small · doi:10.1002/smll.201903254 · Cited by 48
Visible-Light-Activated Molecular Nanomachines Kill Pancreatic Cancer Cells
Ayala‐Orozco, C., Liu, D., Li, Y., Alemany, L. B., Pál, R., Krishnan, S., & Tour, J. M. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b21497 · Cited by 49
Role of Tumor Microenvironment in Cancer Stem Cells Resistance to Radiotherapy
Taeb, S., Ashrafizadeh, M., Zarrabi, A., Rezapoor, S., Musa, A. E., Farhood, B., & Najafi, M. (2021) · Current Cancer Drug Targets · doi:10.2174/1568009622666211224154952 · Cited by 49
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Jiang, Y., Zhao, J., & Zhang, D. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.3c01852 · Cited by 49
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Jiang, N., Song, J., Wang, B., Hua, H., Zhu, H., Guo, X., Xiong, S., & Zhao, Y. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110046 · Cited by 49
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Wang, L., Jiang, W., Liang, X., Li, H., Chen, Z., Liu, Y., Dou, J., Li, S., Wang, Q., Han, W., et al. (2020) · ACS Nano · doi:10.1021/acsnano.0c02674 · Cited by 48
Metal–ligand coordination nanomaterials for radiotherapy: emerging synergistic cancer therapy
Zeng, L., Cao, Y., He, L., Ding, S., Bian, X., & Tian, G. (2020) · Journal of Materials Chemistry B · doi:10.1039/d0tb02294b · Cited by 48
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Wang, M., Li, H., Huang, B., Chen, S., Cui, R., Sun, Z., Zhang, M., & Sun, T. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202100090 · Cited by 48
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Sánchez‐Castillo, A., Vooijs, M., & Kampen, K. R. (2021) · Cancers · doi:10.3390/cancers13061191 · Cited by 47
“Radiation elicits the activation of interconnected processes in the tumor microenvironment, including inflammation, cycling hypoxia, and modulation of cancer-associated fibroblasts, which subsequently lead to immunomodulation, re-vascularization, extracellular matrix remodeling, and fibrosis [123].”
Background
Wnt/β-catenin inhibitor ICG-001 enhances the antitumor efficacy of radiotherapy by increasing radiation-induced DNA damage and improving tumor immune microenvironment in hepatocellular carcinoma
Huang, Y., Sheng, H., Xiao, Y., Hu, W., Zhang, Z., Chen, Y., Zhu, Z., Wu, D., Cao, C., & Sun, J. (2021) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2021.06.034 · Cited by 49
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Hak, C. C. W., Rullan, A., Patin, E. C., Pedersen, M., Melcher, A. A., & Harrington, K. J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.971959 · Cited by 50
Self-citation
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Li, Q., Xu, L., Zhu, J., Zhong, Y., Yang, J., Wang, J., & Tan, H. (2023) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2023/7530794 · Cited by 56
“These changes take place in an interrelated way [27].”
Background
Repeatability of tumour hypoxia imaging using [18F]EF5 PET/CT in head and neck cancer
Silvoniemi, A., Suilamo, S., Laitinen, T., Forsback, S. J., Löyttyniemi, E., Vaittinen, S., Saunavaara, V., Solin, O. H., Grönroos, T. J., & Minn, H. R. I. (2017) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-017-3857-3 · Cited by 47
“Hypoxia is among the strongest biological factors causing radiotherapy (RT) resistance in several types of cancer [1].”
Background
β-Trcp ubiquitin ligase and RSK2 kinase-mediated degradation of FOXN2 promotes tumorigenesis and radioresistance in lung cancer
Ma, J., Lu, Y., Zhang, S., Li, Y., Huang, J., Yin, Z., Ren, J., Huang, K., Liu, L., Yang, K., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-017-0055-6 · Cited by 47
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Ju, C., Wen, Y., Zhang, L., Wang, Q., Xue, L., Shen, J., & Zhang, C. (2019) · Small · doi:10.1002/smll.201905688 · Cited by 47
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“These immunomodulatory effects are observed both locally, in the tumor microenvironment (TME), and systemically, in regional lymph nodes and blood [4,5].”
Background
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Liu, Y., He, D., Xiao, M., Zhu, Y., Zhou, J., & Cao, K. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03523-z · Cited by 48
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Endo, H., Okami, J., Okuyama, H., Nishizawa, Y., Imamura, F., & Inoue, M. (2017) · Oncogene · doi:10.1038/onc.2016.431 · Cited by 50
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Chen, Z., Guan, D., Wang, Z., Li, X., Dong, S., Huang, J., & Zhou, W. (2023) · MedComm · doi:10.1002/mco2.417 · Cited by 47
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Gold nanoparticles enhance anti-tumor effect of radiotherapy to hypoxic tumor
Kim, M. S., Lee, E., Kim, J.-W., Chung, U. S., Koh, W., Keum, K. C., & Koom, W. S. (2016) · Radiation Oncology Journal · doi:10.3857/roj.2016.01788 · Cited by 46
“01788 tumor cells, thereby preventing tumor cell death [4].”
Background
Tumor Immuno-Environment in Cancer Progression and Therapy
Kaliński, P., & Talmadge, J. E. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-67577-0_1 · Cited by 49
PI3K pathway in prostate cancer: All resistant roads lead to PI3K
Park, S., Kim, Y. S., Kim, D. Y., So, I., & Jeon, J. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.09.001 · Cited by 45
X-rays-optimized delivery of radiolabeled albumin for cancer theranostics
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Dimeric Her2-specific affibody mediated cisplatin-loaded nanoparticles for tumor enhanced chemo-radiotherapy
Wang, H., Jia, D., Yuan, D., Yin, X., Yuan, F., Wang, F., Shi, W., Li, H., Zhu, L., & Fan, Q. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-00885-6 · Cited by 46
“For decades, research has focused on the enhancement of RT efficacy by increasing radiation doses, but the severe side effects caused by excessive high-energy radiation to normal tissue and organs are unavoidable [5, 10].”
BackgroundInfluential
Ionizing Radiation Curtails Immunosuppressive Effects From Cancer-Associated Fibroblasts on Dendritic Cells
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Macha, M. A., Rachagani, S., Qazi, A. K., Jahan, R., Gupta, S., Patel, A., Seshacharyulu, P., Lin, C. H., Li, S., Wang, S., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15468 · Cited by 45
“However, determining the radio-sensitizing effects of afatinib using athymic mice would not be appropriate, considering the involvement of the tumor microenvironment (TME) in EGFR signaling [47] and that recent observations suggest that irradiation-induced stromal and immunological changes in the TME determine treatme…”
Background
Metformin for non-small cell lung cancer patients: Opportunities and pitfalls
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Miller, J. P., Borde, B. H., Bordeleau, F., Zanotelli, M. R., LaValley, D. J., Parker, D. J., Bonassar, L. J., Pannullo, S. C., & Reinhart‐King, C. A. (2018) · APL Bioengineering · doi:10.1063/1.5018327 · Cited by 46
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Releasing the brakes of tumor immunity with anti-PD-L1 and pushing its accelerator with L19–IL2 cures poorly immunogenic tumors when combined with radiotherapy
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“8 In addition, RT increases the expression of cellular ligands of activating natural killer (NK) receptors on tumor cells, increasing their anti-tumor cytotoxic activity.”
NONO phase separation enhances DNA damage repair by accelerating nuclear EGFR-induced DNA-PK activation.
Fan, X., Wang, Y., Zhao, W.-W., Bai, S.-M., Ma, Y., Yin, X., Feng, L., Feng, W.-X., Wang, Y., Liu, Q., et al. (2021) · PubMed Central · Cited by 44
Mutual promotion of oxidative stress amplification and calcium overload by degradable spatially selective self-cascade catalyst for synergistic tumor therapy
Wang, X., Li, C., Jin, H., Wang, X., Ding, C., Cao, D., Zhao, L., Deng, G., Lü, J., Wan, Z., et al. (2022) · Chemical Engineering Journal · doi:10.1016/j.cej.2021.134438 · Cited by 45
Response of human macrophages to gamma radiation is mediated via expression of endogenous retroviruses
Mikhalkevich, N., O’Carroll, I. P., Tkavc, R., Lund, K., Sukumar, G., Dalgard, C. L., Johnson, K. R., Li, W., Wang, T., Nath, A., et al. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009305 · Cited by 43
“Macrophages, particularly the anti-inflammatory ones [8], exhibit increased resistance to IR compared to most other immune cells [4,9,10].”
Background
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Chen, S., Yu, S., Du, Z., Huang, X., He, M. S., Long, S., Liu, J., Lan, Y., Yang, D. F., Wang, H., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c02250 · Cited by 44
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Zhuang, Y., Zhao, X., Yuan, B., Zeng, Z., & Chen, Y. (2021) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s300165 · Cited by 44
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Kooreman, E. S., van Houdt, P. J., Keesman, R., van Pelt, V. W. J., Nowee, M. E., Pos, F. J., Sikorska, K., Wetscherek, A., Müller, A., Thorwarth, D., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.705964 · Cited by 44
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Immune microenvironment of cholangiocarcinoma: Biological concepts and treatment strategies
Yu, X., Zhu, L., Wang, T., & Chen, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1037945 · Cited by 45
Modulation of tumor-associated macrophage activity with radiation therapy: a systematic review
Becherini, C., Lancia, A., Detti, B., Lucidi, S., Scartoni, D., Ingrosso, G., Carnevale, M. G., Roghi, M., Bertini, N., Orsatti, C., et al. (2023) · Strahlentherapie und Onkologie · doi:10.1007/s00066-023-02097-3 · Cited by 44
“The interaction with tumor vascularization and immune cells remains crucial [5].”
Background
A bright future: Advanced nanotechnology-assisted microwave therapy
Du, Y., Zhou, J., He, F., Zang, P., Gong, H., Liu, C., & Yang, P. (2023) · Nano Today · doi:10.1016/j.nantod.2023.101963 · Cited by 44
Preclinical Rationale and Clinical Considerations for Radiotherapy Plus Immunotherapy
Schoenhals, J. E., Seyedin, S. N., Tang, C. Z., Cortez, M. A., Niknam, S., Tsouko, E., Chang, J. Y., Hahn, S. M., & Welsh, J. W. (2016) · The Cancer Journal · doi:10.1097/ppo.0000000000000181 · Cited by 46
Magnetic hyperthermia therapy: An emerging modality of cancer treatment in combination with radiotherapy
Pandey, B. N., Shetake, N. G., Balla, M. M. S., & Kumar, A. (2016) · Journal of Radiation and Cancer Research · doi:10.4103/0973-0168.184606 · Cited by 44
A 3D bioinspired highly porous polymeric scaffolding system for in vitro simulation of pancreatic ductal adenocarcinoma
Totti, S., Allenby, M. C., Santos, S. B. D., Mantalaris, A., & Velliou, E. G. (2018) · RSC Advances · doi:10.1039/c8ra02633e · Cited by 44
Harnessing Tumor Microenvironment for Nanoparticle‐Mediated Radiotherapy
Zhu, S., Gu, Z., & Zhao, Y. (2018) · Advanced Therapeutics · doi:10.1002/adtp.201800050 · Cited by 44
Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation
Berzaghi, R., Ahktar, M. A., Islam, A., Pedersen, B. D., Hellevik, T., & Martínez-Zubiaurre, I. (2019) · Cancers · doi:10.3390/cancers11050689 · Cited by 46
“Ionizing radiation leads to significant changes in the tumor stroma, triggering reactions such as acute inflammation, vasculature damage, tumor tissue hypoxia, and fibrosis [5,6,36].”
Background
Vitamin D, gut microbiota, and radiation-related resistance: a love-hate triangle
Huang, R., Xiang, J., & Zhou, P. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1499-y · Cited by 44
“(2015)reported that radiotherapy altered the composition of the gut microbiota, breaking the intestinal barrier and causing apoptosis in intestinal crypts [32], although other studies found no effect of radiation on the gut microbiota.”
Background
Targeting IFN/STAT1 Pathway as a Promising Strategy to Overcome Radioresistance
Liu, S., İmani, S., Deng, Y., Pathak, J. L., Wen, Q., Chen, Y., & Wu, J. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s256708 · Cited by 44
The role of the microbiome in drug resistance in gastrointestinal cancers
Garajová, I., Balsano, R., Wang, H., Leonardi, F., Giovannetti, E., Deng, D., & Peters, G. J. (2020) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2021.1844007 · Cited by 46
Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review
Takahashi, J., & Nagasawa, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239324 · Cited by 44
Advances in Hypofractionated Irradiation-Induced Immunosuppression of Tumor Microenvironment
Wang, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.612072 · Cited by 44
“However, preclinical studies in some tumor models have suggested that radiotherapy-induced changes in the TME may induce an immunosuppressive TME, which may promote tumor invasion and spread in some situations (26, 27).”
Background
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Brandi, N., & Renzulli, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108598 · Cited by 43
X‐Ray‐Induced Drug Release for Cancer Therapy
Liu, H., Zhao, J. L., Xue, Y., Zhang, J., Bai, H., Pan, S., Peng, B., Li, L., & Voelcker, N. H. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202306100 · Cited by 46
The importance of 3D fibre architecture in cancer and implications for biomaterial model design
Ashworth, J., & Cox, T. R. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00704-8 · Cited by 46
Bismuth Sulfide Nanoflowers Facilitated miR339 Delivery to Overcome Stemness and Radioresistance through Ubiquitin-Specific Peptidase 8 in Esophageal Cancer
Zhou, X., Gao, F., Gao, W., Wang, Q., Li, X., Li, X., Li, W., Liu, J., Zhou, H., Luo, A., et al. (2024) · ACS Nano · doi:10.1021/acsnano.4c05100 · Cited by 43
Intelligent Hydrogel-Assisted Hepatocellular Carcinoma Therapy
Tang, Z., Deng, L., Zhang, J., Jiang, T., Xiang, H., Chen, Y., Liu, H., Cai, Z., Cui, W., & Xiong, Y. (2024) · Research · doi:10.34133/research.0477 · Cited by 46
Nitric Oxide‐Releasing Nanoscale Metal‐Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy
Xiong, Y., Li, J., Jiang, X., Zhen, W., Ma, X., & Lin, W. (2025) · Advanced Science · doi:10.1002/advs.202413518 · Cited by 43
Analyzing Tumor Metabolism In Vivo
Faubert, B., & DeBerardinis, R. J. (2016) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050216-121954 · Cited by 44
“Hypoxic tumors are associated with therapeutic resistance and enhanced metastatic potential (Barker et al. 2015).”
Background
Autophagy induced by ionizing radiation promotes cell death over survival in human colorectal cancer cells
Classen, F., Kranz, P., Riffkin, H., Pompsch, M., Wolf, A., Göpelt, K., Baumann, M., Baumann, J., Brockmeier, U., & Metzen, E. (2018) · Experimental Cell Research · doi:10.1016/j.yexcr.2018.11.004 · Cited by 46
Cinnamaldehyde enhances apoptotic effect of oxaliplatin and reverses epithelial-mesenchymal transition and stemnness in hypoxic colorectal cancer cells
Wu, C., Zhuang, Y., Zhou, J., Liu, S., Wang, R., & Shu, P. (2019) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.111500 · Cited by 43
Therapeutic modulators of hepatic stellate cells for hepatocellular carcinoma
Ruan, Q., Wang, H., Burke, L. J., Bridle, K. R., Li, X., Zhao, C., Crawford, D. H., Roberts, M. S., & Liang, X. (2020) · International Journal of Cancer · doi:10.1002/ijc.32899 · Cited by 43
“TGF-β signaling is upregulated by radiotherapy and is a key regulator of HSC activation in the TME.(12) TGF-β activated by radiation promotes the production of profibrotic cytokines and stimulates HSCs, by overproduction of plasminogen activator inhibitor-1, one of the downstream targets of TGF-β.”
BackgroundInfluential
Basics and Frontiers on Pancreatic Cancer for Radiation Oncology: Target Delineation, SBRT, SIB Technique, MRgRT, Particle Therapy, Immunotherapy and Clinical Guidelines
Cellini, F., ARCELLI, A., Simoni, N., Caravatta, L., Buwenge, M., Calabrese, A., Brunetti, O., Genovesi, D., Mazzarotto, R., Deodato, F., et al. (2020) · Cancers · doi:10.3390/cancers12071729 · Cited by 43
“In fact, the anticancer effect of RT not only relies on DNA damage but also is based on the interaction with the host immune system, regulating several steps of immune response, such as T cell priming, antigen exposure and presentation [159,160].”
Background
Injectable Nanocomposite Hydrogels for Cancer Therapy
Du, W., Zong, Q., Guo, R., Ling, G., & Zhang, P. (2021) · Macromolecular Bioscience · doi:10.1002/mabi.202100186 · Cited by 43
HSP90 inhibition suppresses tumor glycolytic flux to potentiate the therapeutic efficacy of radiotherapy for head and neck cancer
Chen, F., Tang, C., Yang, F., Ekpenyong, A., Qin, R., Xie, J., Momen‐Heravi, F., Saba, N. F., & Teng, Y. (2024) · Science Advances · doi:10.1126/sciadv.adk3663 · Cited by 43
“Activated dendritic cells play a pivotal role in presenting tumor antigens to T cells, thereby aiding in the recognition of cancer cells ( 35 , 36 ).”
Influential
Lactate and cancer: spinal metastases and potential therapeutic targets (part 2)
Pennington, Z. A., Goodwin, M. L., Westbroek, E. M., Cottrill, E. J., Ahmed, A. K., & Sciubba, D. M. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.01.85 · Cited by 44
Natural killer cells as a promising therapeutic target for cancer immunotherapy
Kim, N., Lee, H. H., Lee, H.-J., Choi, W. S., Lee, J., & Kim, H. S. (2019) · Archives of Pharmacal Research · doi:10.1007/s12272-019-01143-y · Cited by 44
mTOR-Mediated Antioxidant Activation in Solid Tumor Radioresistance
Woo, Y., Lee, H.-J., Jung, Y. M., & Jung, Y. (2019) · Journal of Oncology · doi:10.1155/2019/5956867 · Cited by 42
“ese upregulated genes are closely related to survival mechanisms, such as DNA repair, metabolic changes, tumor recurrence, and malignant transformation [9].”
Background
Tumor microenvironment, immune response and post-radiotherapy tumor clearance
Koukourakis, M. I., & Giatromanolaki, A. N. (2020) · Clinical & Translational Oncology · doi:10.1007/s12094-020-02378-8 · Cited by 43
“Hypoxia and acidity are, therefore, directly interrelated and actively contribute to the creation of a tumor microenvironment barrier to the activity of radiotherapy and chemotherapy [24].”
Background
Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy
Marcus, D., Lieverse, R. I. Y., Klein, C., Abdollahi, A., Lambin, P., Dubois, L. J., & Yaromina, A. (2021) · Cancers · doi:10.3390/cancers13061468 · Cited by 43
“A dose of 8–16 Gy led to upregulation of acid sphingomyelinase (ASMase), which induced endothelial cell apoptosis and triggered immune responses through increased production of cytokines/chemokines that induce immune cell recruitment [74].”
Background
Comprehensive Pneumonitis Profile of Thoracic Radiotherapy Followed by Immune Checkpoint Inhibitor and Risk Factors for Radiation Recall Pneumonitis in Lung Cancer
Lu, X., Wang, J., Zhang, T., Zhou, Z., Deng, L., Wang, X., Wang, W., Liu, W., Tang, W., Wang, Z., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.918787 · Cited by 43
Dll1-Mediated Notch Signaling Drives Tumor Cell Cross-talk with Cancer-Associated Fibroblasts to Promote Radioresistance in Breast Cancer
Nandi, A., Debnath, R., Nayak, A., To, T. K. J., Thacker, G., Reilly, M., Gumber, S., Karagounis, I. V., Li, N., Lengner, C. J., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-1225 · Cited by 43
Mechano-modulation of T cells for cancer immunotherapy
Hyun, J., Kim, S. J., Cho, S., & Kim, H. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122101 · Cited by 40
Risks of leukemia, intracranial tumours and lymphomas in childhood and early adulthood after pediatric radiation exposure from computed tomography
Wang, W.-H., Sung, C., Wang, S., & Shao, Y. J. (2023) · Canadian Medical Association Journal · doi:10.1503/cmaj.221303 · Cited by 41
EISA in Tandem with ICD to Form In Situ Nanofiber Vaccine for Enhanced Tumor Radioimmunotherapy
Luo, H., Cao, H., Jia, H., Shang, Y., Liu, J., Gui, H., Yang, C., Ren, C., Wang, Z., & Liu, J. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202301083 · Cited by 42

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.
ORCID: Barker, Holly E.
Paget, James T. E.
Khan, Aadil A.
Harrington, Kevin J.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2015-06-24
Volume: 15
Issue: 7
Pages: 409-425
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc3958
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence

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