The DOI matches its Crossref record; 200 of the 200 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Cited by
Sorted by citations
Items 401–500 of 1,005
Combining radiation plus immunotherapy to improve systemic immune response
Cushman, T. R., Gomez, D. R., Kumar, R., Likacheva, A., Chang, J. Y., Cadena, A. P., Paris, S., & Welsh, J. W. (2018) · Journal of Thoracic Disease · doi:10.21037/jtd.2018.01.130 · Cited by 61
“While the re lat ionship between radiat ion and immunotherapies and tumor stroma remains poorly understood, it is well established that CAFs and low TSR are associated with radioresistance and poor systemic drug penetration to tumor sites (31,36).”
BackgroundTuyaerts, S., Nuffel, A. M. T. V., Naert, E., van Dam, P. A., Vuylsteke, P., Caluwé, A. D., Aspeslagh, S., Dirix, P. R., Lippens, L., Jaeghere, E. A. D., et al. (2019) · BMC Cancer · doi:10.1186/s12885-019-5676-3 · Cited by 62
Radiation as an In Situ Auto-Vaccination: Current Perspectives and Challenges
Goto, T. (2019) · Vaccines · doi:10.3390/vaccines7030100 · Cited by 64
“Various cytokines are induced by radiation [69].”
Song, S., Chen, Q., Li, Y., Lei, G., Scott, A. W., Huo, L., Li, C. Y., Estrella, J. S., Correa, A. M., Pizzi, M. P., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-321175 · Cited by 62
Manganese dioxide (MnO2) based nanomaterials for cancer therapies and theranostics
Zhu, D. Y., Zhu, X., Ren, S., Lu, Y., & Zhu, H. (2020) · Journal of drug targeting · doi:10.1080/1061186x.2020.1815209 · Cited by 61
“Under cancer radiotherapy, hypoxic tumour tissues have a tendency to be more resistant to ionising radiation than well-oxygenated tumour tissues, because the DNA damage induced by stable radiation needs O2 [58,59].”
BackgroundZhu, L., Zhao, Y., Liu, T., Chen, M., Qian, W. P., Jiang, B., Barwick, B. G., Zhang, L., Styblo, T. M., Li, X., et al. (2022) · ACS Nano · doi:10.1021/acsnano.2c07440 · Cited by 63
Bio‐Inspired Antioxidant Heparin‐Mimetic Peptide Hydrogel for Radiation‐Induced Skin Injury Repair
Hao, Y., Li, H., Guo, J., Wang, D., Zhang, J., Liu, J., Yang, C., Zhang, Y., Li, G., & Liu, J. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202203387 · Cited by 61
New horizons for the therapeutic application of nanozymes in cancer treatment
Malla, P., Wang, Y., & Su, C. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03185-5 · Cited by 63
“However, the unique characteristics of the tumor microenvironment (TME), including conditions of hypoxia and elevated levels of hydrogen peroxide (H 2 O 2 ), significantly hinder the therapeutic efficacy of these chemotherapeutic agents [96, 97].”
Li, Y., Cho, M. H., Lee, S. S., Lee, D.-E., Cheong, H., & Choi, Y. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.06.025 · Cited by 61
Emerging roles of HSF1 in cancer: Cellular and molecular episodes
Wang, G., Cao, P., Fan, Y., & Tan, K. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188390 · Cited by 64
Microbiota transplantation: Targeting cancer treatment
Wu, X., Zhang, T., Chen, X., Ji, G., & Zhang, F. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.03.010 · Cited by 63
Schumacher, O., Galvao, D. A., Taaffe, D. R., Chee, R., Spry, N. A., & Newton, R. U. (2020) · Prostate Cancer and Prostatic Diseases · doi:10.1038/s41391-020-0245-z · Cited by 64
Fenton metal nanomedicines for imaging-guided combinatorial chemodynamic therapy against cancer
Liu, P., Peng, Y., Ding, J., & Zhou, W. (2021) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2021.10.003 · Cited by 60
CAR-T Plus Radiotherapy: A Promising Combination for Immunosuppressive Tumors
Qin, V. M., Haynes, N. M., D’Souza, C., Neeson, P. J., & Zhu, J. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.813832 · Cited by 61
Watson, S. S., Duc, B., Kang, Z., de Tonnac, A., Eling, N., Font, L., Whitmarsh, T., Massara, M., Joyce, J. A., Watson, S. S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47185-9 · Cited by 61
“another critical aspect is how the tumor microenvironment (TME) responds to IR, as this can modulate the ef fi cacy of IR through several mechanisms 14 – 16 .”
BackgroundCancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis
Fernández‐Nogueira, P., Fuster, G., Gutiérrez-Uzquiza, Á., Gascón, P., Carbó, N., & Bragado, P. (2021) · Cancers · doi:10.3390/cancers13133146 · Cited by 59
“However, radiotherapy (RT) usually results in fibrosis, which may lead to survival and RT resistance of cancer cells [38,39] (Figure 1 and Table S3).”
BackgroundLiu, J., Niu, N., Li, X., Zhang, X., & Sood, A. K. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.10.005 · Cited by 63
Wang, X., Zhang, Y., Mu, X., Tu, C. R., Chung, Y., Tsao, S. W., Chan, G., Leung, W. H., Lau, Y., Liu, Y., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003832 · Cited by 61
“9 10 Therefore, it is urgent to develop new therapeutic strategies that synergize with radiotherapy and overcome an immunosuppressive NPC microenvironment.”
Jiang, J., Wang, W., Zheng, H., Chen, X., Liu, X., Xie, Q., Cai, X., Zhang, Z., & Li, R. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121561 · Cited by 60
Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor
Wen, J., Luo, Y., Gao, H., Zhang, L., Wang, X., Huang, J., Shang, T., Zhou, D., Wang, D., Wang, Z., et al. (2021) · Journal of Nanobiotechnology · doi:10.1186/s12951-021-01196-6 · Cited by 59
“Clinical studies have proven that hypoxia is one of the main features that lead to the resistance to radiotherapy and chemotherapy [8, 9].”
BackgroundZhang, T., You, P., Suo, M., Lyu, M., Lam, J. W. Y., Jin, Z., Ning, S., & Tang, B. Z. (2023) · Advanced Science · doi:10.1002/advs.202304042 · Cited by 59
Molecular determinants of immunogenic cell death elicited by radiation therapy
Galassi, C., Klapp, V., Yamazaki, T., & Galluzzi, L. (2023) · Immunological Reviews · doi:10.1111/imr.13271 · Cited by 65
“67,213,214 222 In this setting, it will be crucial not only to adapt conventional RT approaches to limit local and systemic immunosuppression, but also identify novel, therapeutically relevant targets to extend the intrinsic immunostimulatory effects of RT.”
Visualizing vasculature and its response to therapy in the tumor microenvironment
Lin, Q., Choyke, P. L., & Sato, N. (2023) · Theranostics · doi:10.7150/thno.84947 · Cited by 68
“The effects of radiation therapy (RT) on blood vessels highly depend on the radiation dose, timing, fraction size, as well as the type, location, and stage of the cancer [161-163].”
BackgroundGuo, D., Xu, S., Wang, N., Jiang, H., Huang, Y., Jin, X., Bai, X., Zhang, C., & Zhu, X. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.08.032 · Cited by 59
Wu, C.-J., Tsai, Y.-T., Lee, I., Wu, P., Lu, L., Tsao, W.-S., Huang, Y.-J., Chang, C.-C., Ka, S., & Tao, M. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1477459 · Cited by 59
Sexual Dimorphism of Gut Microbiota Dictates Therapeutics Efficacy of Radiation Injuries
Cui, M., Xiao, H., Li, Y., Zhang, S., Dong, J., Wang, B., Zhu, C., Jiang, M., Zhu, T., He, J., et al. (2019) · Advanced Science · doi:10.1002/advs.201901048 · Cited by 59
Update on immune checkpoint inhibitors in gynecological cancers
Heong, V. Y. M., Ngoi, N. Y. L., & Tan, D. S. P. (2016) · Journal of Gynecologic Oncology · doi:10.3802/jgo.2017.28.e20 · Cited by 59
“Radiation and chemotherapeutics can lead to upregulation of neoantigens to activate the adaptive immune system and enhance tumor cell immunogenicity [105].”
BackgroundXu, X., Gong, X., Wang, Y., Li, J., Wang, H., Wang, J., Sha, X., Li, Y., & Zhang, Z. (2020) · Advanced Therapeutics · doi:10.1002/adtp.201900181 · Cited by 59
Nanomaterials for radiotherapeutics-based multimodal synergistic cancer therapy
Yang, X., Gao, L., Guo, Q., Li, Y., Ma, Y., Yang, J., Gong, C., & Cheng, Y. (2020) · Nano Research · doi:10.1007/s12274-020-2722-z · Cited by 58
Bláha, P., Feoli, C., Agosteo, S., Calvaruso, M., Cammarata, F. P., Catalano, R., Ciocca, M., Cirrone, G. A. P., Conte, V., Cuttone, G., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.682647 · Cited by 58
“On the other hand, the relative biological effectiveness (RBE) at tumor cell killing of clinical protons is similar to that of CRT (4), hence PT offers no obvious advantage against cancer radioresistance, a major cause of treatment failure (5).”
BackgroundThe role of the bacterial microbiome in the treatment of cancer
Yu, Z., Xie, R., You, R., Liu, Y., Chen, X.-Y., Chen, M., & Huang, P.-Y. (2021) · BMC Cancer · doi:10.1186/s12885-021-08664-0 · Cited by 57
“Radiotherapy can also induce apoptosis of intestinal cells and cause damage to the gut microbiome composition [52], leading to intestinal inflammation, which may cause diarrhoea and fatigue [53, 54].”
BackgroundIrradiation causes senescence, ATP release, and P2X7 receptor isoform switch in glioblastoma
Zanoni, M., Sarti, A. C., Zamagni, A., Cortesi, M., Pignatta, S., Arienti, C., Tebaldi, M., Sarnelli, A., Romeo, A., Bartolini, D., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04526-0 · Cited by 62
“Radiotherapy deeply impacts TME biochemical composition inducing an accumulation of DAMPs including eATP [11].”
BackgroundThioredoxin reductase: An emerging pharmacologic target for radiosensitization of cancer
Patwardhan, R. S., Sharma, D., & Sandur, S. K. (2022) · Translational Oncology · doi:10.1016/j.tranon.2022.101341 · Cited by 58
“This leads to tumor recurrence and metastasis and impacts cancer patients’ progression-free survival and quality of life [1].”
BackgroundModulating tumor physical microenvironment for fueling CAR-T cell therapy
Luo, Z. Y., Yao, X., Li, M., Fang, D., Fei, Y., Cheng, Z., Xu, Y., & Zhu, B. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114301 · Cited by 59
Pan, P., Dong, X., Chen, Y., Ye, J., Sun, Y., & Zhang, X. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121810 · Cited by 59
Sharma, P., & Otto, M. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.08.022 · Cited by 59
Combining Oncolytic Adenovirus with Radiation—A Paradigm for the Future of Radiosensitization
O'Cathail, S. M., Pokrovska, T. D., Maughan, T., Fisher, K. D., Seymour, L. W., & Hawkins, M. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00153 · Cited by 58
“Effects on different cell types and the tumor microenvironment have recently been elegantly reviewed elsewhere and an in-depth discussion is outwith the scope of this article (53, 55, 60).”
BackgroundDaecher, A., Stanczak, M., Liu, J., Zhang, J., Du, S., Forsberg, F., Leeper, D. B., & Eisenbrey, J. R. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.09.037 · Cited by 58
“The abnormal structure of tumor vasculature and decreased perfusion often creates areas of hypoxia within the tumor microenvironment and is a significant contributing factor to radiotherapy resistance that develops within tumors [19].”
BackgroundInvestigations into the cancer stem cell niche using in-vitro 3-D tumor models and microfluidics
Sreepadmanabh, M., & Toley, B. J. (2018) · Biotechnology Advances · doi:10.1016/j.biotechadv.2018.03.009 · Cited by 58
Supramolecular Radiosensitizer Based on Hypoxia‐Responsive Macrocycle
Hou, X., Chang, Y., Yue, Y., Wang, Z.-H., Ding, F., Li, Z., Li, H., Xu, Y., Kong, X., Huang, F., et al. (2022) · Advanced Science · doi:10.1002/advs.202104349 · Cited by 57
Qiao, L., Chen, Y., Liang, N., Xie, J. W., Deng, G., Chen, F., Wang, X., Liu, F., Li, Y., & Zhang, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.775238 · Cited by 58
Wu, J., Chan, Y.-T., Lu, Y., Wang, N., & Feng, Y. (2023) · Medicinal Research Reviews · doi:10.1002/med.21967 · Cited by 56
Recent advances in mitochondria‐targeting theranostic agents
Qian, K., Gao, S., Jiang, Z., Ding, Q., & Cheng, Z. (2024) · Exploration · doi:10.1002/exp.20230063 · Cited by 59
Crosstalk between CAFs and tumour cells in head and neck cancer
Li, X., González-Maroto, C., & Tavassoli, M. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02053-9 · Cited by 61
“Moreover, CAFs are considered to be responsible for increased resistance to radiotherapy, chemotherapy, targeted therapy, and immune therapy [25, 90, 115, 176].”
BackgroundEmergence of miR-34a in radiation therapy
Lacombe, J., & Zenhausern, F. (2016) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2016.11.017 · Cited by 57
“The progressive and perpetuating proliferative phase prevents tissue resolution and results in the development of RIF (Barker et al., 2015).”
InfluentialTopical Fibronectin Improves Wound Healing of Irradiated Skin
Johnson, M. B., Pang, B., Gardner, D. J., Niknam‐Bienia, S., Soundararajan, V., Bramos, A., Perrault, D. P., Banks, K. C., Lee, G. K., Baker, R. Y., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-03614-y · Cited by 57
Total abdominal irradiation exposure impairs cognitive function involving miR-34a-5p/BDNF axis
Cui, M., Xiao, H., Li, Y., Dong, J., Luo, D., Li, H., Feng, G., Wang, H., & Fan, S. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.06.021 · Cited by 59
“Radiotherapy is a cornerstone of modern management of malignancies and, > 50% of patients with cancer receive this treatment at some point in the course of their disease [4].”
BackgroundEffects of radiation on the metastatic process
Sundahl, N., Duprez, F., Ost, P., Neve, W. D., & Mareel, M. M. K. (2018) · Molecular Medicine · doi:10.1186/s10020-018-0015-8 · Cited by 60
“It is highly probable that therapeutic manipulation of one ecosystem affects the others, a phenomenon that needs to be analyzed in view of the increasing cellular and molecular complexity of therapy responses (Barker et al., 2015).”
BackgroundCytoreductive treatment strategies for de novo metastatic prostate cancer
Connor, M. J., Shah, T. T., Horan, G., Bevan, C. L., Winkler, M. H., & Ahmed, H. U. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0284-3 · Cited by 56
Oxygen Nanoshuttles for Tumor Oxygenation and Enhanced Cancer Treatment
Feng, L., Betzer, O., Tao, D., Sadan, T., Popovtzer, R., & Liu, Z. (2019) · CCS Chemistry · doi:10.31635/ccschem.019.20190010 · Cited by 56
The role of tumor microenvironment and exosomes in dormancy and relapse
Attaran, S., & Bissell, M. J. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.09.008 · Cited by 57
Elzoghby, A. O., Samir, O., Emam, H. E., Soliman, A., Abdelgalil, R. M., Elmorshedy, Y. M., Elkhodairy, K. A., & Nasr, M. L. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.03.022 · Cited by 57
“Comparison of different ICD inducer strategies are summarized in Table 3 60,62,66,67,74,80,172,177 e 189 .”
Yao, Y., Xu, R., Shao, W., Tan, J., Wang, S., Chen, S., Zhuang, A., Liu, X., & Jia, R. (2024) · Advanced Science · doi:10.1002/advs.202403107 · Cited by 56
Lu, L., Li, F., Gao, Y., Kang, S., Li, J., & Guo, J. (2024) · Molecular Medicine · doi:10.1186/s10020-024-00873-0 · Cited by 60
“Following radiotherapy, the tumor releases numerous tumor antigens, activating antigen-presenting cells and facilitating immune cell infiltration when combined with the immune-enhancing effects of certain bacterial or bacterial derivative compounds [35].”
BackgroundZhang, T., Yu, H., Ni, C., Zhang, T., Liu, L., Lv, Q., Zhang, Z., Wang, Z., Wu, D., Wu, P., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-04978-x · Cited by 58
Xu, J., Saklatvala, R., Mittal, S., Deshmukh, S., & Procopio, A. T. (2020) · Advanced Science · doi:10.1002/advs.201903394 · Cited by 57
Ott, M., Kassab, C., Marisetty, A., Hashimoto, Y., Wei, J., Zamler, D. B., Leu, J.-S., Tomaszowski, K.-H., Sabbagh, A., Fang, D., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-4092 · Cited by 56
“2, 4), the propensity for tumor recurrence in patients with GBM is very high, with little improvement of patient median survival time (5, 6).”
BackgroundThe roles of CC chemokines in response to radiation
Wang, L., Jiang, J., Chen, Y., Jia, Q., & Chu, Q. (2022) · Radiation Oncology · doi:10.1186/s13014-022-02038-x · Cited by 55
“Most research on improving the efficacy of RT has focused on tumour cells [4].”
BackgroundChemotherapy-induced metastasis: molecular mechanisms and clinical therapies
Su, J.-X., Li, S.-J., Zhou, X., Zhang, Z., Yu, Y., Liu, S.-L., & Qi, Q. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01093-8 · Cited by 56
“It is noted that single-dose radiotherapy has limitations; it can cause inflammation, cycling hypoxia, immunomodulation, revascularization, CAF-coordinated ECM remodeling, and fibrosis in the TME [139].”
BackgroundChisholm, J., Mandeville, H., Adams, M., Minard-Collin, V., Rogers, T., Kelsey, A., Shipley, J., van Rijn, R., de Vries, I. S. A., van Ewijk, R., et al. (2024) · Cancers · doi:10.3390/cancers16050998 · Cited by 52
“…a significant proportion of the irradiated tissue will be removed surgically, which may reduce the risk of second tumours; there is a biological rationale as the tumour and surrounding tissues are less hypoxic than in the postoperative setting, and hypoxia increases tumour radio-resistance [54].”
BackgroundT cell exhaustion in cancer: Mechanisms and clinical implications
Wang, J., Xu, Y., Huang, Z., & Lu, X. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26645 · Cited by 56
“Although, radiotherapy was once thought to just cause immunosuppressive effect and support tumor-specific immunity similar with chemotherapy, it actually leads to the activation of a series of immune process including activation of tumor-associated dendritic cells, increased expression of tumor-associated antigens and…”
Wu, C., Muroski, M. E., Miska, J. M., Lee-Chang, C., Shen, Y., Rashidi, A., Zhang, P., Xiao, T., Han, Y., Lopez‐Rosas, A., et al. (2018) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2018.11.015 · Cited by 55
Xiao, X., Wang, Y., Chen, J., Qin, P., Chen, P., Zhou, D., & Pan, Y. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121793 · Cited by 54
Intratumoral microbiota: A new force in diagnosing and treating pancreatic cancer
Jiang, Z., Zhang, W., Zhang, Z., Sha, G., Wang, D., & Tang, D. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.216031 · Cited by 58
Programming the lifestyles of engineered bacteria for cancer therapy
Fu, S., Zhang, R., Gao, Y., Xiong, J., Li, Y., Pu, L., Xia, A., & Jin, F. (2023) · National Science Review · doi:10.1093/nsr/nwad031 · Cited by 55
“The hypoxia and immune-privileged tumor microenvironment is one of the biggest obstacles in the way of many cancer therapeutics [1–3], such as chemotherapy [4], radiotherapy [5] and immunotherapy [6,7].”
BackgroundAdvances in nanoparticle-based radiotherapy for cancer treatment
He, M., Chen, S., Yu, H., Fan, X., Wu, H., Wang, Y., Wang, H., & Yin, X. (2024) · iScience · doi:10.1016/j.isci.2024.111602 · Cited by 54
“140 Meng et al. designed a smart drug delivery system based on MnO 2 NPs, delivering the HIF-1 inhibitor acriflavine (ACF) to tumor (ACF@MnO 2 ).”
Near-Infrared Light-Responsive Nitric Oxide Delivery Platform for Enhanced Radioimmunotherapy
Zhou, X., Meng, Z., She, J., Zhang, Y., Yi, X., Zhou, H., Zhong, J., Dong, Z., Han, X., Chen, M., et al. (2020) · Nano-Micro Letters · doi:10.1007/s40820-020-00431-3 · Cited by 54
Dual effects of active ERK in cancer: A potential target for enhancing radiosensitivity (Review)
Lu, Y., Liu, B., Liu, Y., Yu, X., & Cheng, G. (2020) · Oncology Letters · doi:10.3892/ol.2020.11684 · Cited by 55
“Although RT has demonstrated various degrees of success, recurrence and treatment failure may occur in patients due to intrinsic or external radioresistance (3).”
BackgroundScarred Lung. An Update on Radiation-Induced Pulmonary Fibrosis
Jarzebska, N., Karetnikova, E. S., Markov, A. G., Kasper, M. E., Rodionov, R. N., & Spieth, P. M. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2020.585756 · Cited by 54
Leveraging macrophages for cancer theranostics
Liu, L., Li, H., Wang, J., Zhang, J., Liang, X., Guo, W., & Gu, Z. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114136 · Cited by 53
Radiotherapy resistance: identifying universal biomarkers for various human cancers
Larionova, I., Rakina, M. A., Ivanyuk, E. E., Trushchuk, Y. M., Чернышова, А. Л., & Denisov, E. V. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-03923-4 · Cited by 53
Deciphering the Biological Effects of Radiotherapy in Cancer Cells
Zhou, L., Zheng, X., Ding, C., Zou, Z., Liang, Y., Zhou, Y., & Li, X. (2022) · Biomolecules · doi:10.3390/biom12091167 · Cited by 57
“mechanisms of radioresistance mediated by the tumor stroma [12,13].”
BackgroundHou, M., Su, H., Wu, Q., Sun, W., Zhang, P., Jiang, Y., Qian, K., & Zhang, C. (2023) · Advanced Functional Materials · doi:10.1002/adfm.202212510 · Cited by 54
Wang, Y., Wang, Y., Pan, J., Gan, L., & Xue, J. (2023) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2023.109689 · Cited by 54
Radiation Therapy and Myeloid-Derived Suppressor Cells: Breaking Down Their Cancerous Partnership
Bergerud, K. B., Berkseth, M., Pardoll, D. M., Ganguly, S., Kleinberg, L. R., Lawrence, J., Odde, D. J., Largaespada, D. A., Terezakis, S. A., & Sloan, L. (2023) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2023.11.050 · Cited by 62
“30,31 Cancer skews the differentiation of myeloid cells toward cancer-supportive phenotypes, such as MDSCs. 29 MDSC counts are elevated in patients with cancer compared with healthy individuals and correlate with cancer stage and disease recurrence status.”
BackgroundInfluentialLin, Z., Li, G., Jiang, K., Li, Z., & Liu, T. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02106-8 · Cited by 57
“Recent work has indicated that radiation can mediate the contents and secretion of functional exosomes from cancer cells and other cell types within tumor microenvironment, resulting in radiotherapy resistance and radiation-induced bystander effects [92, 93].”
BackgroundLuo, J., Sun, T., Liu, Z., Liu, Y., Liu, J., Wang, S., Shi, X., & Zhou, H. (2025) · International Journal of Oral Science · doi:10.1038/s41368-025-00380-w · Cited by 61
“11 These diverse senescent cells possess the capacity to sustain and intensify the TISnt state through well-established mechanisms such as senescence-associated secretory phenotype (SASP), mitochondrial dysfunction or altered cellular communications, 12 along with unique pathways involving speci fi…”
Zhu, H., Cao, X., Cai, X., Tian, Y., Wang, D., Qi, J., Teng, Z., Lu, G., Ni, Q., Wang, S., et al. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119677 · Cited by 53
Cancer-Associated Fibroblasts: Implications for Cancer Therapy
Maia, A. R. R., & Wiemann, S. (2021) · Cancers · doi:10.3390/cancers13143526 · Cited by 58
Wang, B., Liu, W., Liu, C., Du, K., Guo, Z., Zhang, G., Huang, Z., Lin, S., Cen, B., Tian, Y., et al. (2022) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2022.12.029 · Cited by 54
Active Ingredients from Chinese Medicine for Combination Cancer Therapy
Wang, X., Li, J., Chen, R., Li, T., & Chen, M. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.77720 · Cited by 52
“However, radiotherapy can cause incomplete tumor ablation and trigger a response in the TME, which may promote radioresistance and tumor metastasis [176].”
Cancer-associated fibroblasts: tumor defenders in radiation therapy
Zhang, Y., Lv, N., Li, M., Liu, M., & Wu, C. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06060-z · Cited by 52
“CAFs promote radioresistance Despite several advances in RT over previous decades, radioresistance remains an unresolved issue in cancer therapy [60].”
BackgroundLee, L. C., & Lo, K. K. (2024) · Small Methods · doi:10.1002/smtd.202400563 · Cited by 52
Piper, M., Mueller, A. C., & Karam, S. D. (2020) · Molecular Carcinogenesis · doi:10.1002/mc.23205 · Cited by 52
Sequential catalytic nanomedicine augments synergistic chemodrug and chemodynamic cancer therapy
Liang, R., Chen, Y., Huo, M., Zhang, J., & Li, Y. (2019) · Nanoscale Horizons · doi:10.1039/c9nh00008a · Cited by 51
Park, S., Joung, J., Min, Y. W., Nam, J., Ryu, D., Oh, D., Park, W., Lee, S. K., Choi, Y., Ahn, J. S., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0609-x · Cited by 53
Park, M., Kwon, J., Kong, J., Moon, S. M., Cho, S., Yang, K. Y., Jang, W. I., Kim, M., Kim, Y., & Shin, U. S. (2021) · Cancers · doi:10.3390/cancers13153760 · Cited by 54
“In radiotherapy, vascular, stromal, and immunological changes in T-ME induced by radiation promote radioresistance and tumor recurrence; furthermore, radiotherapy has recently been proposed to target the T-ME to overcome radioresistance [39].”
BackgroundWang, C., Sun, X., Feng, L., & Liu, Z. (2024) · BMEMat · doi:10.1002/bmm2.12083 · Cited by 52
Alberti, D., Protti, N., Franck, M., Stefanìa, R., Bortolussi, S., Altieri, S., Deagostino, A., Aime, S., & Crich, S. G. (2017) · ChemMedChem · doi:10.1002/cmdc.201700039 · Cited by 51
Shi, F., Wang, X., Teng, F., Kong, L., & Yu, J. (2017) · Cancer Biology & Therapy · doi:10.1080/15384047.2016.1276133 · Cited by 51
“1).(3,8) This may elucidate the formation of abscopal response.”
BackgroundGrinde, M. T., Vik, J., Camilio, K. A., Martínez-Zubiaurre, I., & Hellevik, T. (2017) · Scientific Reports · doi:10.1038/srep46714 · Cited by 51
Tumour radiosensitivity is associated with immune activation in solid tumours
Ström, T., Harrison, L. B., Giuliano, A. R., Schell, M. J., Eschrich, S. A., Berglund, A., Fulp, W. J., Thapa, R., Coppola, D., Kim, S., et al. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2017.08.001 · Cited by 51
Zhou, J., Xue, C., Hou, Y., Li, M., Hu, Y., Chen, Q., Li, Y., Li, K., Song, G., Cai, K., et al. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.01.002 · Cited by 51
microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation
Labbé, M., Hoey, C., Ray, J., Potiron, V. A., Supiot, S., Liu, S. K., & Fradin, D. D. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01186-6 · Cited by 52
Trial Watch—Small molecules targeting the immunological tumor microenvironment for cancer therapy
Buqué, A., Bloy, N., Aranda, F., Cremer, I., Eggermont, A. M. M., Fridman, W. H., Fucikova, J. P., Galon, J., Špíšek, R., Tartour, É., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1149674 · Cited by 50
“acquisition of immunostimulatory versus immunosuppressive functions.(228-231) One strategy to suppress immunosuppressive”
BackgroundRadiotherapy and Cytokine Storm: Risk and Mechanism
Zhang, C., Liang, Z., Ma, S., & Liu, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.670464 · Cited by 57
Cancer Stem‐Like Cells‐Oriented Surface Self‐Assembly to Conquer Radioresistance
Wang, Q., Cao, H., Hou, X., Wang, D., Wang, Z., Shang, Y., Zhang, S., Liu, J., Ren, C., & Liu, J. (2023) · Advanced Materials · doi:10.1002/adma.202302916 · Cited by 51
Azeez, S. S., Yashooa, R. K., Smail, S., Salihi, A., Ali, A. S., Mamand, S., & Janson, C. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02386-8 · Cited by 56
“RT can counteract the immunosuppressive TME by normalising the tumour vasculature, reducing hypoxia, and decreasing the presence of immunosuppressive cells [377].”
MicroRNAs Involvement in Radioresistance of Head and Neck Cancer
Ahmad, P., Šáňa, J., Slavík, M., Šlampa, P., Smilek, P., & Slabý, O. (2017) · Disease Markers · doi:10.1155/2017/8245345 · Cited by 50
“The aim of this review is to summarize present knowledge about radioresistance of HNSCC with emphasis on role of miRNAs in this tumor phenomenon.”
BackgroundLoka, R. S., Yu, F., Sletten, E. T., & Nguyen, H. M. (2017) · Chemical Communications · doi:10.1039/c7cc04156j · Cited by 49
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
