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

Show all 200 references

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Items 101–200 of 1,005

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Li, J., Luo, Y., & Pu, K. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202008386 · Cited by 223
Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma
Zhang, T., Ren, Y., Yang, P., Wang, J., & Zhou, H. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05351-1 · Cited by 240
“Furthermore, due to the complex tumour microenvironment (TME), pancreatic cancer exhibits significant resistance to radiotherapy [4].”
Background
Nanoscale‐Coordination‐Polymer‐Shelled Manganese Dioxide Composite Nanoparticles: A Multistage Redox/pH/H2O2‐Responsive Cancer Theranostic Nanoplatform
Liu, J., Chen, Q., Zhu, W., Yi, X., Yang, Y. P., Dong, Z., & Liu, Z. (2017) · Advanced Functional Materials · doi:10.1002/adfm.201605926 · Cited by 221
Multifunctional Graphdiyne–Cerium Oxide Nanozymes Facilitate MicroRNA Delivery and Attenuate Tumor Hypoxia for Highly Efficient Radiotherapy of Esophageal Cancer
Zhou, X., You, M., Wang, F., Wang, Z., Gao, X., Jing, C., Liu, J., Guo, M., Li, J., Luo, A., et al. (2021) · Advanced Materials · doi:10.1002/adma.202100556 · Cited by 220
Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer
Petroni, G., Cantley, L. C., Santambrogio, L., Formenti, S. C., & Galluzzi, L. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00579-w · Cited by 224
Modeling radiation injury-induced cell death and countermeasure drug responses in a human Gut-on-a-Chip
Jalili-Firoozinezhad, S., Prantil-Baun, R., Jiang, A., Potla, R., Mammoto, T., Weaver, J. C., Ferrante, T. C., Kim, H. J., Cabral, J. M. S., Levy, O., et al. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0304-8 · Cited by 209
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Cheng, W., Kang, K., Zhao, A., & Wu, Y. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01581-2 · Cited by 229
Systemic immune responses to irradiated tumours via the transport of antigens to the tumour periphery by injected flagellate bacteria
Wang, W., Xu, H., Ye, Q., Tao, F., Wheeldon, I. R., Yuan, A., Hu, Y., & Wu, J. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00834-6 · Cited by 212
Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities
Pinto, A. T., Pinto, M. L., Cardoso, A. P., Monteiro, C. F., Pinto, M. T., Maia, A. F., Castro, P., Figueira, R., Monteiro, A., Marques, M., et al. (2016) · Scientific Reports · doi:10.1038/srep18765 · Cited by 220
Role of neutrophil extracellular traps in radiation resistance of invasive bladder cancer
Shinde-Jadhav, S., Mansure, J. J., Rayes, R. F., Marcq, G., Ayoub, M., Skowronski, R., Kool, R., Bourdeau, F., Brimo, F., Spicer, J. D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23086-z · Cited by 215
CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion
Günaydın, G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.668349 · Cited by 211
ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment
Dillon, M. T., Bergerhoff, K. F., Pedersen, M., Whittock, H., Crespo-Rodriguez, E., Patin, E. C., Pearson, A., Smith, H. G., Paget, J. T.-E. H., Patel, R., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1821 · Cited by 208
“At the same time, increasing recognition of the effect of the vasculature and stroma on tumor control and normal tissue side-effects of radiotherapy has highlighted potential new targets for intervention (2).”
BackgroundSelf-citation
Modulating tumor hypoxia by nanomedicine for effective cancer therapy
Jahanban‐Esfahlan, R., de la Guardia, M., Ahmadi, D., & Yousefi, B. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.25859 · Cited by 201
“So they act as oxygen consumers and exacerbate the hypoxia condition in tumors, culminating in resistance to therapy accompanied by developing an irreversible metastatic potential (Barker et al., 2015; Henderson and Fingar, 1987).”
Background
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Lan, Y., Moustafa, M., Knoll, M., Xu, C., Furkel, J., Lazorchak, A. S., Yeung, T.-L., Hasheminasab, S.-M., Jenkins, M. H., Meister, S., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.08.008 · Cited by 211
Unveiling the active sites on ferrihydrite with apparent catalase-like activity for potentiating radiotherapy
Zhang, R., Chen, L., Liang, Q. Y., Xi, J., Zhao, H., Jin, Y., Gao, X., Yan, X., Gao, L., & Fan, K. (2021) · Nano Today · doi:10.1016/j.nantod.2021.101317 · Cited by 203
A Dual Immunotherapy Nanoparticle Improves T‐Cell Activation and Cancer Immunotherapy
Mi, Y., Smith, C. C., Yang, F., Qi, Y., Roche, K. C., Serody, J. S., Vincent, B. G., & Wang, A. Z. (2018) · Advanced Materials · doi:10.1002/adma.201706098 · Cited by 200
Gut Microbiota Shapes the Efficiency of Cancer Therapy
Ma, W., Mao, Q., Xia, W., Dong, G., Yu, C., & Jiang, F. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01050 · Cited by 200
CD73 on cancer-associated fibroblasts enhanced by the A2B-mediated feedforward circuit enforces an immune checkpoint
Yu, M., Guo, G. F., Huang, L., Deng, L., Chang, C.-S., Achyut, B. R., Canning, M. T., Xu, N., Arbab, A. S., Bollag, R. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14060-x · Cited by 196
Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity
Donlon, N., Power, R. F., Hayes, C., Reynolds, J. V., & Lysaght, J. (2021) · Cancer Letters · doi:10.1016/j.canlet.2020.12.045 · Cited by 199
“The tumour vasculature and endothelial cells are perhaps the most well studied component of TME following radiation, but changes depend on dose, fractionation, as well as the type and location of the tumour [10].”
Background
Interfering with Tumor Hypoxia for Radiotherapy Optimization
Telarović, I., Wenger, R. H., & Pruschy, M. N. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02000-x · Cited by 208
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Wang, X., Zhang, C., Du, J., Dong, X., Jian, S., Yan, L., Gu, Z., & Zhao, Y. (2019) · ACS Nano · doi:10.1021/acsnano.9b01818 · Cited by 187
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Hak, A., Ali, M. S., Sankaranarayanan, S. A., Shinde, V. R., & Rengan, A. K. (2023) · ACS Applied Bio Materials · doi:10.1021/acsabm.2c00891 · Cited by 186
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Fan, W., Tang, W., Lau, J., Shen, Z., Xie, J., Shi, J., & Chen, X. S. (2019) · Advanced Materials · doi:10.1002/adma.201806381 · Cited by 181
Core–shell Au@MnO2 nanoparticles for enhanced radiotherapy via improving the tumor oxygenation
Yi, X., Chen, L., Zhong, X., Gao, R., Qian, Y., Wu, F., Song, G., Chai, Z., Liu, Z., & Yang, K. (2016) · Nano Research · doi:10.1007/s12274-016-1205-8 · Cited by 181
“Almost 50% of patients with cancer undergo RT at least once during their treatment course [1].”
Nanoparticle-enhanced radiotherapy synergizes with PD-L1 blockade to limit post-surgical cancer recurrence and metastasis
Guan, X., Sun, L., Shen, Y., Jin, F.-S., Bo, X., Zhu, C., Han, X., Li, X., Chen, Y., Xu, H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30543-w · Cited by 190
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Li, J. J. X., Tsang, J. Y., & Tse, G. M.-K. (2021) · Cancers · doi:10.3390/cancers13164233 · Cited by 190
“Lysyl oxidase (LOX) and integrins are also implicated in radiation-induced fibrosis [73,99].”
Background
Nanoparticle‐Mediated Radiotherapy Remodels the Tumor Microenvironment to Enhance Antitumor Efficacy
Zhen, W., Weichselbaum, R. R., & Lin, W. (2022) · Advanced Materials · doi:10.1002/adma.202206370 · Cited by 188
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Jiang, W., Chan, C. K. F., Weissman, I. L., Kim, B. Y. S., & Hahn, S. M. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.09.007 · Cited by 179
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Mi, Y., Hagan, C. T., Vincent, B. G., & Wang, A. Z. (2019) · Advanced Science · doi:10.1002/advs.201801847 · Cited by 178
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Gulley, J. L., Schlom, J., Barcellos‐Hoff, M. H., Wang, X., Seoane, J., Audhuy, F., Lan, Y., Dussault, I., & Moustakas, A. (2021) · Molecular Oncology · doi:10.1002/1878-0261.13146 · Cited by 182
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Deng, Z., Xi, M., Zhang, C., Wu, X., Li, Q., Wang, C., Fang, H., Sun, G., Zhang, Y., Yang, G., et al. (2023) · ACS Nano · doi:10.1021/acsnano.2c10352 · Cited by 180
Molecular targeting of hypoxia in radiotherapy
Rey, S., Schito, L., Koritzinsky, M., & Wouters, B. G. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.10.002 · Cited by 178
“sion and responses to therapy (reviewed in [366]).”
Background
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Huo, D., Liu, S., Zhang, C., He, J., Zhou, Z., Zhang, H., & Hu, Y. (2017) · ACS Nano · doi:10.1021/acsnano.7b04737 · Cited by 171
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Cao, Z., & Liu, J. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.07.009 · Cited by 168
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“Research into improving outcomes from RT focused almost entirely on the cancer cell itself, ignoring complex biological interactions between the tumor and its environment that it colonizes (15).”
Background
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Ali, M. Y., Oliva, C. R., Noman, A. S. M., Allen, B. G., Goswami, P. C., Zakharia, Y., Monga, V., Spitz, D. R., Buatti, J. M., & Griguer, C. E. (2020) · Cancers · doi:10.3390/cancers12092511 · Cited by 183
Immune Landscape of Colorectal Cancer Tumor Microenvironment from Different Primary Tumor Location
Zhang, L., Zhao, Y., Dai, Y., Cheng, J., Gong, Z., Feng, Y., Sun, C., Jia, Q., & Zhu, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01578 · Cited by 172
Targeting cancer‐related inflammation in the era of immunotherapy
Nakamura, K., & Smyth, M. J. (2016) · Immunology and Cell Biology · doi:10.1038/icb.2016.126 · Cited by 164
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Farhood, B., Khodamoradi, E., Hoseini‐Ghahfarokhi, M., Motevaseli, E., Mirtavoos‐Mahyari, H., Musa, A. E., & Najafi, M. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104745 · Cited by 172
Molecular mechanisms of hypoxia in cancer
Challapalli, A., Carroll, L. S., & Aboagye, E. O. (2017) · Clinical and Translational Imaging · doi:10.1007/s40336-017-0231-1 · Cited by 167
“Irradiation also induces changes in the tumour microenvironment such as vascular, stromal, and immunological changes which may promote radioresistance and tumour recurrence [77].”
Background
Immune targets in the tumor microenvironment treated by radiotherapy
Ozpiskin, O. M., Zhang, L., & Li, J. J. (2019) · Theranostics · doi:10.7150/thno.32648 · Cited by 163
“stromal cells in the irradiated local microenvironment as well as the cells distant to the tumor [4, 5].”
BackgroundInfluential
Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging
Muñoz, D. P., Yannone, S. M., Daemen, A., Sun, Y., Vakar-Lopez, F., Kawahara, M., Freund, A. M., Rodier, F., Wu, J. D., Desprez, P.-Y., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.124716 · Cited by 162
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Application of nanotechnology to cancer radiotherapy
Mi, Y., Shao, Z., Vang, J., Kaidar‐Person, O., & Wang, A. Z. (2016) · Cancer Nanotechnology · doi:10.1186/s12645-016-0024-7 · Cited by 155
Targeting immune checkpoints in breast cancer: an update of early results
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Menon, H., Ramapriyan, R., Cushman, T. R., Verma, V., Kim, H. H., Schoenhals, J. E., Atalar, S. C., Selek, U., Chun, S. G., Chang, J. Y., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00193 · Cited by 160
Combination of radiotherapy and suppression of Tregs enhances abscopal antitumor effect and inhibits metastasis in rectal cancer
Ji, D., Song, C., Li, Y., Xia, J., Wu, Y., Jia, J., Cui, X., Yu, S., & Gu, J. F. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000826 · Cited by 158
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Shim, M. K., Yang, S., Sun, I., & Kim, K. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114177 · Cited by 158
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Wang, Y., Ma, K., Kang, M., Yan, D., Niu, N., Yan, S., Sun, P., Zhang, L., Sun, L., Wang, D., et al. (2024) · Chemical Society Reviews · doi:10.1039/d4cs00708e · Cited by 162
Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors
Derer, A., Frey, B., Fietkau, R., & Gaipl, U. S. (2015) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-015-1771-8 · Cited by 155
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Strategies based on metal-based nanoparticles for hypoxic-tumor radiotherapy
Zhang, C., Yan, L., Gu, Z., & Zhao, Y. (2019) · Chemical Science · doi:10.1039/c9sc02107h · Cited by 146
Impact of (chemo)radiotherapy on immune cell composition and function in cervical cancer patients
van Meir, H., Nout, R. A., Welters, M. J. P., Loof, N. M., de Kam, M. L., van Ham, J. J., Samuels, S., Kenter, G. G., Cohen, A. F., Melief, C. J. M., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2016.1267095 · Cited by 143
“to treatment success or failure, particularly in so-called immunogenic tumors.(8) Interestingly, it was shown that a pretreatment peripheral blood lymphocyte count at or above the median value was associated with higher clinical responses and survival rates.”
Background
Clinical Advances of Hypoxia-Activated Prodrugs in Combination With Radiation Therapy
Mistry, I. N., Thomas, M., Calder, E. D. D., Conway, S. J., & Hammond, E. M. (2017) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2017.03.024 · Cited by 145
Reactive oxygen species-powered cancer immunotherapy: Current status and challenges
He, M., Wang, M., Xu, T., Zhang, M., Dai, H., Wang, C., Ding, D., & Zhong, Z. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.02.040 · Cited by 147
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Luen, S. J., Savas, P. S., Fox, S. B., Salgado, R., & Loi, S. (2017) · Pathology · doi:10.1016/j.pathol.2016.10.010 · Cited by 137
Dancing with reactive oxygen species generation and elimination in nanotheranostics for disease treatment
Zhou, Z., Ni, K., Deng, H., & Chen, X. S. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.006 · Cited by 139
Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer
Fokas, E., Ströbel, P., Fietkau, R., Ghadimi, M. B., Liersch, T., Grabenbauer, G. G., Hartmann, A., Kaufmann, M., Sauer, R., Graeven, U., et al. (2017) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djx095 · Cited by 143
“Accordingly, pathophysiological mechanisms, such as hypoxia and angiogenesis (22), oncogenic activation (23), epithelial-mesenchymal transition (24), and resistance to apoptosis, (25) result in local tumor resistance to CRT and increase the propensity to develop metastases.”
Background
Radiotherapy and anti-PD-1/PD-L1 combinations in lung cancer: building better translational research platforms
Kordbacheh, T., Honeychurch, J., Blackhall, F. H., Finn, C. F., & Illidge, T. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx790 · Cited by 145
Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects
Shaked, Y. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.57 · Cited by 137
Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy
Baran, N., & Konopleva, M. Y. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0895 · Cited by 143
“HAPs and DNA damage signaling Chronic hypoxia has been found to induce activation of DNAdependent protein kinase (DNA-PK) in the absence of applied DNA damage, and this activation was found to promote stabilization of HIF1a and to increase therapy resistance and treatment failure (57).”
Background
Cancer-associated fibroblasts in radiotherapy: challenges and new opportunities
Wang, Z., Tang, Y., Tan, Y., Wei, Q., & Yu, W. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0362-2 · Cited by 142
“The secretome of CAFs from human non-small cell lung carcinoma was ent (TME) including cycling hypoxia, immune modulation, vascular st into senescence-like fibroblasts, which share similar characteristics E. High levels of TGF-β1 was detected in conditioned media from e expression in radiation treated fibroblasts are…”
BackgroundInfluential
Engineering a Therapy‐Induced “Immunogenic Cancer Cell Death” Amplifier to Boost Systemic Tumor Elimination
Li, B., Hao, G., Sun, B. F., Gu, Z., & Xu, Z. P. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909745 · Cited by 136
Generation of hydroxyl radical-activatable ratiometric near-infrared bimodal probes for early monitoring of tumor response to therapy
Wu, L., Ishigaki, Y., Zeng, W., Harimoto, T., Yin, B., Chen, Y., Liao, S., Liu, Y., Sun, Y., Zhang, X., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26380-y · Cited by 136
Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review
Mortezaee, K., Najafi, M., Farhood, B., Ahmadi, A., Potes, Y., Shabeeb, D., & Musa, A. E. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.05.009 · Cited by 138
Priming anti-tumor immunity by radiotherapy: Dying tumor cell-derived DAMPs trigger endothelial cell activation and recruitment of myeloid cells
Krombach, J., Hennel, R., Brix, N., Orth, M., Schötz, U., Ernst, A., Schuster, J., Zuchtriegel, G., Reichel, C. A., Bierschenk, S., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1523097 · Cited by 138
“In addition to its direct tumoricidal effects, radiotherapy is known to induce distinct changes in the tumor microenvironment, particularly in the leukocyte compartment.(38) Meanwhile, it is well acknowledged that anti-tumor immune mechanisms can be stimulated by radiotherapy in the sense of an in situ cancer vaccinat…”
Background
Radiotherapy for renal cell carcinoma: renaissance of an overlooked approach
Siva, S., Kothari, G., Muacevic, A., Louie, A. V., Slotman, B. J., Teh, B. S., & Lo, S. S.-M. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2017.87 · Cited by 132
Interfacial engineering of gold nanoclusters for biomedical applications
Srinivasulu, Y. G., Yao, Q., Goswami, N., & Xie, J. (2020) · Materials Horizons · doi:10.1039/d0mh00827c · Cited by 134
NF‐κB targeting for overcoming tumor resistance and normal tissues toxicity
Mortezaee, K., Najafi, M., Farhood, B., Ahmadi, A., Shabeeb, D., & Musa, A. E. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28504 · Cited by 130
“In the tumor, NF‐κB can be upregulated by different signaling pathways after exposing tumor cells to radiation or chemotherapy, and then modulates several reactions within malignant cells (Barker et al., 2015; Bradford & Baldwin, 2014; Taniguchi & Karin, 2018).”
Background
Scintillator-Based Nanohybrids with Sacrificial Electron Prodrug for Enhanced X-ray-Induced Photodynamic Therapy
Wang, H., Lv, B., Tang, Z., Zhang, M., Ge, W., Liu, Y., He, X., Zhao, K., Zheng, X., He, M., et al. (2018) · Nano Letters · doi:10.1021/acs.nanolett.8b02409 · Cited by 130
Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications
Buqué, A., Bloy, N., Aranda, F., Castoldi, F., Eggermont, A. M. M., Cremer, I., Fridman, W. H., Fucikova, J. P., Galon, J., Marabelle, A., et al. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1008814 · Cited by 132
Overcoming Resistance to Combination Radiation-Immunotherapy: A Focus on Contributing Pathways Within the Tumor Microenvironment
Darragh, L. B., Oweida, A., & Karam, S. D. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03154 · Cited by 133
Recent developments in mesoporous polydopamine-derived nanoplatforms for cancer theranostics
Zhu, M., Shi, Y., Shan, Y., Guo, J., Song, X., Wu, Y., Wu, M., Lü, Y., Chen, W., Xu, X., et al. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-01131-9 · Cited by 128
Nanoparticles-mediated reoxygenation strategy relieves tumor hypoxia for enhanced cancer therapy
Wang, H., Li, J., Wang, Y., Gong, X., Xu, X., Wang, J., Li, Y., Sha, X., & Zhang, Z. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.12.028 · Cited by 129
Precise Subcellular Organelle Targeting for Boosting Endogenous‐Stimuli‐Mediated Tumor Therapy
Zhen, W., An, S., Wang, S., Hu, W., Li, Y., Jiang, X., & Li, J. (2021) · Advanced Materials · doi:10.1002/adma.202101572 · Cited by 127
Overview of recent advances in liposomal nanoparticle-based cancer immunotherapy
Gao, A., Hu, X., Saeed, M., Chen, B., Li, Y., & Yu, H. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0281-1 · Cited by 125
“A majority of tumors may be eliminated by applying these methods; however, metastasis and subsequent recurrences remain a formidable challenge in the clinic [1, 2].”
Background
D-arginine-loaded metal-organic frameworks nanoparticles sensitize osteosarcoma to radiotherapy
Du, C., Zhou, M., Jia, F., Ruan, L., Lu, H., Zhang, J., Zhu, B., Liu, X., Chen, J., Chai, Z., et al. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2020.120642 · Cited by 127
Suppression of local type I interferon by gut microbiota–derived butyrate impairs antitumor effects of ionizing radiation
Yang, K., Hou, Y., Zhang, Y., Liang, H. L., Sharma, A., Zheng, W., Wang, L., Torres, R., Tatebe, K., Chmura, S. J., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20201915 · Cited by 128
Hybrid Manganese Dioxide Nanoparticles Potentiate Radiation Therapy by Modulating Tumor Hypoxia
Abbasi, A. Z., Gordijo, C. R., Amini, M. A., Maeda, A., Rauth, A. M., DaCosta, R. S., & Wu, X. Y. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3475 · Cited by 121
Calcium Bisphosphonate Nanoparticles with Chelator-Free Radiolabeling to Deplete Tumor-Associated Macrophages for Enhanced Cancer Radioisotope Therapy
Tian, L., Yi, X., Dong, Z., Xu, J., Liang, C., Chao, Y., Wang, Y., Yang, K., & Liu, Z. (2018) · ACS Nano · doi:10.1021/acsnano.8b06699 · Cited by 122
A hybrid semiconducting organosilica-based O2 nanoeconomizer for on-demand synergistic photothermally boosted radiotherapy
Tang, W., Yáng, Z., He, L., Deng, L., Fathi, P., Zhu, S., Li, L., Shen, B., Wang, Z., Jacobson, O., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20860-3 · Cited by 122
Triggering Sequential Catalytic Fenton Reaction on 2D MXenes for Hyperthermia-Augmented Synergistic Nanocatalytic Cancer Therapy
Liang, R., Li, Y., Huo, M., Lin, H., & Chen, Y. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b13598 · Cited by 121
Biomedical applications of MnO2 nanomaterials as nanozyme-based theranostics
Sisakhtnezhad, S., Rahimi, M., & Mohammadi, S. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114833 · Cited by 127
Albumin‐Templated Manganese Dioxide Nanoparticles for Enhanced Radioisotope Therapy
Tian, L., Chen, Q., Yi, X., Chen, J., Liang, C., Chao, Y., Yang, K., & Liu, Z. (2017) · Small · doi:10.1002/smll.201700640 · Cited by 119
Epigenetic control of macrophage polarization: implications for targeting tumor-associated macrophages
de Groot, A. E., & Pienta, K. J. (2018) · Oncotarget · doi:10.18632/oncotarget.24556 · Cited by 124
“Research has suggested that the TME plays a critical role in recurrence [6, 7].”
Background
Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?
Villéger, R., Lopès, A., Carrier, G., Véziant, J., Billard, E., Barnich, N., Gagnière, J., Vazeille, E., & Bonnet, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184584 · Cited by 125
“[62] underlined the triggering of a releasing of inflammatory cytokines such as IL-1 and TNF-α and immune cell recruitment after treatment.”
Background
Tumor-targeted hybrid protein oxygen carrier to simultaneously enhance hypoxia-dampened chemotherapy and photodynamic therapy at a single dose
Luo, Z., Tian, H., Liu, L., Chen, Z., Liang, R., Chen, Z., Wu, Z., Ma, A.-Q., Zheng, M., & Cai, L. (2018) · Theranostics · doi:10.7150/thno.25409 · Cited by 121
“For instance, hyperbaric oxygen chambers have been clinically utilized to force more oxygen into the blood and the tumor when patients undergo cancer therapies [19-22].”
Background
Cyclic Hypoxia: An Update on Its Characteristics, Methods to Measure It and Biological Implications in Cancer
Bader, S. B., Dewhirst, M. W., & Hammond, E. M. (2020) · Cancers · doi:10.3390/cancers13010023 · Cited by 127
Targeting senescence-like fibroblasts radiosensitizes non–small cell lung cancer and reduces radiation-induced pulmonary fibrosis
Meng, J., Li, Y., Wan, C., Sun, Y., Dai, X., Huang, J., Hu, Y. W., Gao, Y., Wu, B., Zhang, Z., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.146334 · Cited by 129
Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment
Eguchi, T., Sogawa, C. A., Okusha, Y., Uchibe, K., Iinuma, R., Ono, K., Nakano, K., Murakami, J., Itoh, M., Arai, K., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0191109 · Cited by 123
“Tumors are often resistant to immunity [13], chemotherapy [14, 15] and radiation therapy [16] due to clonal evolution which generates multiple variant genotypes and thus novel phenotypes in cancer cells [17–20].”
Background
Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6+ cancer cell and macrophage polarization
Choi, S., Kim, A.-R., Nam, J.-K., Kim, J., Kim, J.-Y., Seo, H. R., Lee, H., Cho, J., & Lee, Y. (2018) · Nature Communications · doi:10.1038/s41467-018-07470-w · Cited by 125
Microbiota in cancer development and treatment
Raza, M. H., Gul, K., Arshad, A., Riaz, N., Waheed, U., Rauf, A., Aldakheel, F. M., Alduraywish, S. A., Rehman, M. U., Abdullah, M., et al. (2018) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-018-2816-0 · Cited by 122
Poly(amidoamine) Dendrimer-Coordinated Copper(II) Complexes as a Theranostic Nanoplatform for the Radiotherapy-Enhanced Magnetic Resonance Imaging and Chemotherapy of Tumors and Tumor Metastasis
Fan, Y., Zhang, J., Shi, M., Li, D., Lü, C., Cao, X., Peng, C., Mignani, S. M., Majoral, J., & Shi, X. (2019) · Nano Letters · doi:10.1021/acs.nanolett.8b04757 · Cited by 118
Turning “Cold” Into “Hot” Tumors—Opportunities and Challenges for Radio-Immunotherapy Against Primary and Metastatic Brain Cancers
Sevenich, L. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00163 · Cited by 121
“Radiation Modulates the Cellular Composition of the Tumor Microenvironment and Affects Effector Functions of Immune Cells Another important factor that determines synergy of radioimmunotherapy is the cellular composition of the tumor microenvironment (156).”
Background
Quercetin-Modified Metal–Organic Frameworks for Dual Sensitization of Radiotherapy in Tumor Tissues by Inhibiting the Carbonic Anhydrase IX
Ma, T., Liu, Y., Wu, Q., Luo, L., Cui, Y., Wang, X., Chen, X., Tan, L., & Meng, X. (2019) · ACS Nano · doi:10.1021/acsnano.8b09221 · Cited by 117

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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