Where Innovations Meets Personalized and Precision Medicine

Managing Inflammation in Cancer Therapy: Effects of Inflammation Control on Metastasis and Treatment Response

Document Type : Review Article

Authors

1 Department of Biology, Faculty of Basic Sciences, Science & Research Branch, Islamic Azad University, Tehran, Iran.

2 Department of Pediatrics, Bohlool Hospital, Gonabad University of Medical Sciences, Gonabad, Iran.

Abstract
Chronic inflammation is a pivotal element in the onset and advancement of cancer. It is crucial in tumor initiation, survival, metastasis, and therapeutic resistance. This study seeks to thoroughly examine the intricate relationship between inflammation and cancer, emphasizing the role of inflammatory processes in tumor formation and their influence on cancer therapy responses. We will investigate the molecular processes behind inflammation-induced cancer progression, analyze how inflammation affects metastasis, and assess its effects on the effectiveness of treatments like chemotherapy, immunotherapy, and targeted therapies. Furthermore, we will investigate prospective therapeutic approaches for addressing inflammation in cancer treatment, emphasizing the necessity for specific modulation to enhance treatment efficacy while mitigating adverse consequences such as immune suppression or heightened infection risk. The report finishes with a discussion on prospective research avenues focused on optimizing inflammation-targeting techniques to augment the efficacy of cancer therapies and better patient outcomes. Ultimately, a deeper understanding of inflammation’s dual role in cancer could pave the way for innovative, more personalized treatment strategies that improve survival and quality of life for patients.

Keywords

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1.Tripathi S, Sharma Y, Kumar D. Unveiling the link between chronic inflammation and cancer. Metabolism Open. 2025;25:100347.
2.Greten FR, Grivennikov SI. Inflammation and Cancer: Triggers, Mechanisms, and Consequences. Immunity. 2019;51(1):27-41.
3.Xie Y, Liu F, Wu Y, Zhu Y, Jiang Y, Wu Q, et al. Inflammation in cancer: therapeutic opportunities from new insights. Molecular Cancer. 2025;24(1):51.
4.Pęczek P, Gajda M, Rutkowski K, Fudalej M, Deptała A, Badowska-Kozakiewicz AM. Cancer-associated inflammation: pathophysiology and clinical significance. Journal of cancer research and clinical oncology. 2023;149(6):2657-72.
5.Zhao H, Wu L, Yan G, Chen Y, Zhou M, Wu Y, et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal transduction and targeted therapy. 2021;6(1):263.
6.Hibino S, Kawazoe T, Kasahara H, Itoh S, Ishimoto T, Sakata-Yanagimoto M, et al. Inflammation-Induced Tumorigenesis and Metastasis. International Journal of Molecular Sciences [Internet]. 2021; 22(11).
7.Nishida A, Andoh A. The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis. Cells. 2025;14(7).
8.Zhang S, Xiao X, Yi Y, Wang X, Zhu L, Shen Y, et al. Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets. Signal transduction and targeted therapy. 2024;9(1):149.
9.Hirano T. IL-6 in inflammation, autoimmunity and cancer. International immunology. 2021;33(3):127-48.
10.Joshi DC, Sharma A, Prasad S, Singh K, Kumar M, Sherawat K, et al. Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy. Discover oncology. 2024;15(1):342.
11.Li Z, Li J, Bai X, Huang X, Wang Q. Tumor microenvironment as a complex milieu driving cancer progression: a mini review. Clinical and Translational Oncology. 2025;27(5):1943-52.
12.Wang D-R, Wu X-L, Sun Y-L. Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response. Signal transduction and targeted therapy. 2022;7(1):331.
13.Liu Y, Liang J, Zhang Y, Guo Q. Drug resistance and tumor immune microenvironment: An overview of current understandings (Review). International journal of oncology. 2024;65(4).
14.Liu J, Jiao X, Ma D, Fang Y, Gao Q. CAR-T therapy and targeted treatments: Emerging combination strategies in solid tumors. Med. 2024;5(6):530-49.
15.Albini A, Di Paola L, Mei G, Baci D, Fusco N, Corso G, et al. Inflammation and cancer cell survival: TRAF2 as a key player. Cell Death & Disease. 2025;16(1):292.
16.Capece D, Verzella D, Flati I, Arboretto P, Cornice J, Franzoso G. NF-κB: blending metabolism, immunity, and inflammation. Trends in Immunology. 2022;43(9):757-75.
17.Guo Q, Jin Y, Chen X, Ye X, Shen X, Lin M, et al. NF-κB in biology and targeted therapy: new insights and translational implications. Signal transduction and targeted therapy. 2024;9(1):53.
18.Lv Y, Chen C, Han M, Tian C, Song F, Feng S, et al. CXCL2: a key player in the tumor microenvironment and inflammatory diseases. Cancer cell international. 2025;25(1):133.
19.Nishida A, Andoh A. The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis. Cells [Internet]. 2025; 14(7).
20.Naghavi M, Mestrovic T, Gray A, Gershberg Hayoon A, Swetschinski LR, Robles Aguilar G, et al. Global burden associated with 85 pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet Infectious Diseases. 2024;24(8):868-95.
21.Yu Y, Liu S, Yang L, Song P, Liu Z, Liu X, et al. Roles of reactive oxygen species in inflammation and cancer. MedComm. 2024;5(4):e519.
22.Chan H-W, Kuo D-Y, Shueng P-W, Chuang H-Y. Visualizing the Tumor Microenvironment: Molecular Imaging Probes Target Extracellular Matrix, Vascular Networks, and Immunosuppressive Cells. Pharmaceuticals [Internet]. 2024; 17(12).
23.Zhao Y, Shen M, Wu L, Yang H, Yao Y, Yang Q, et al. Stromal cells in the tumor microenvironment: accomplices of tumor progression? Cell Death Dis. 2023;14(9):587.
24.Liu Z, Chen J, Ren Y, Liu S, Ba Y, Zuo A, et al. Multi-stage mechanisms of tumor metastasis and therapeutic strategies. Signal transduction and targeted therapy. 2024;9(1):270.
25.Huang R, Kang T, Chen S. The role of tumor-associated macrophages in tumor immune evasion. Journal of cancer research and clinical oncology. 2024;150(5):238.
26.Ghalehbandi S, Yuzugulen J, Pranjol MZI, Pourgholami MH. The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF. European Journal of Pharmacology. 2023;949:175586.
27.Ji ZZ, Chan MK, Chan AS, Leung KT, Jiang X, To KF, et al. Tumour-associated macrophages: versatile players in the tumour microenvironment. Frontiers in cell and developmental biology. 2023;11:1261749.
28.Xiong S, Dong L, Cheng L. Neutrophils in cancer carcinogenesis and metastasis. Journal of hematology & oncology. 2021;14(1):173.
29.Tsioumpekou M, Krijgsman D, Leusen JHW, Olofsen PA. The Role of Cytokines in Neutrophil Development, Tissue Homing, Function and Plasticity in Health and Disease. Cells. 2023;12(15).
30.Chavda V, Chaurasia B, Garg K, Deora H, Umana GE, Palmisciano P, et al. Molecular mechanisms of oxidative stress in stroke and cancer. Brain Disorders. 2022;5:100029.
31.Zhao Y, Ye X, Xiong Z, Ihsan A, Ares I, Martínez M, et al. Cancer Metabolism: The Role of ROS in DNA Damage and Induction of Apoptosis in Cancer Cells. Metabolites. 2023;13(7).
32.Zhou X, An B, Lin Y, Ni Y, Zhao X, Liang X. Molecular mechanisms of ROS-modulated cancer chemoresistance and therapeutic strategies. Biomedicine & Pharmacotherapy. 2023;165:115036.
33.Chen S, Saeed AFUH, Liu Q, Jiang Q, Xu H, Xiao GG, et al. Macrophages in immunoregulation and therapeutics. Signal transduction and targeted therapy. 2023;8(1):207.
34.Haddadin L, Sun X. Stem Cells in Cancer: From Mechanisms to Therapeutic Strategies. Cells [Internet]. 2025; 14(7).
35.Zhu Q, Zhang R, Zhao Z, Xie T, Sui X. Harnessing phytochemicals: Innovative strategies to enhance cancer immunotherapy. Drug Resistance Updates. 2025;79:101206.
36.Pote MS, Singh D, M. A A, Suchita J, Gacche RN. Cancer metastases: Tailoring the targets. Heliyon. 2024;10(15):e35369.
37.Yi M, Li T, Niu M, Zhang H, Wu Y, Wu K, et al. Targeting cytokine and chemokine signaling pathways for cancer therapy. Signal transduction and targeted therapy. 2024;9(1):176.
38.Ribatti D, Tamma R, Annese T. Epithelial-Mesenchymal Transition in Cancer: A Historical Overview. Translational Oncology. 2020;13(6):100773.
39.Giblin MJ, Ontko CD, Penn JS. Effect of cytokine-induced alterations in extracellular matrix composition on diabetic retinopathy-relevant endothelial cell behaviors. Scientific reports. 2022;12(1):12955.
40.Pan C, Wang X, Yang C, Fu K, Wang F, Fu L. The culture and application of circulating tumor cell-derived organoids. Trends in Cell Biology. 2025;35(5):364-80.
41.Beheshtizadeh N, Gharibshahian M, Bayati M, Maleki R, Strachan H, Doughty S, et al. Vascular endothelial growth factor (VEGF) delivery approaches in regenerative medicine. Biomedicine & Pharmacotherapy. 2023;166:115301.
42.Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nature Communications. 2020;11(1):5120.
43.Liu Z-L, Chen H-H, Zheng L-L, Sun L-P, Shi L. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal transduction and targeted therapy. 2023;8(1):198.
44.El-Tanani M, Rabbani SA, Babiker R, Rangraze I, Kapre S, Palakurthi SS, et al. Unraveling the tumor microenvironment: Insights into cancer metastasis and therapeutic strategies. Cancer Letters. 2024;591:216894.
45.Behranvand N, Nasri F, Zolfaghari Emameh R, Khani P, Hosseini A, Garssen J, et al. Chemotherapy: a double-edged sword in cancer treatment. Cancer immunology, immunotherapy : CII. 2022;71(3):507-26.
46.Luo H, Liu L, Liu X, Xie Y, Huang X, Yang M, et al. Interleukin-33 (IL-33) promotes DNA damage-resistance in lung cancer. Cell Death Dis. 2025;16(1):274.
47.Zhao Z, Li T, Sun L, Yuan Y, Zhu Y. Potential mechanisms of cancer-associated fibroblasts in therapeutic resistance. Biomedicine & Pharmacotherapy. 2023;166:115425.
48.Sipos F, Műzes G. Cancer Stem Cell Relationship with Pro-Tumoral Inflammatory Microenvironment. Biomedicines. 2023;11(1).
49.Ghemrawi R, Abuamer L, Kremesh S, Hussien G, Ahmed R, Mousa W, et al. Revolutionizing Cancer Treatment: Recent Advances in Immunotherapy. Biomedicines. 2024;12(9).
50.Cha JH, Chan LC, Li CW, Hsu JL, Hung MC. Mechanisms Controlling PD-L1 Expression in Cancer. Molecular cell. 2019;76(3):359-70.
51.Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nature Reviews Immunology. 2020;20(11):651-68.
52.Hu A, Sun L, Lin H, Liao Y, Yang H, Mao Y. Harnessing innate immune pathways for therapeutic advancement in cancer. Signal transduction and targeted therapy. 2024;9(1):68.
53.Di Spirito A, Balkhi S, Vivona V, Mortara L. Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies. Exploration of targeted anti-tumor therapy. 2025;6:1002304.
54.Yu H, Li J, Peng S, Liu Q, Chen D, He Z, et al. Tumor microenvironment: Nurturing cancer cells for immunoevasion and druggable vulnerabilities for cancer immunotherapy. Cancer Letters. 2025;611:217385.
55.Mai Z, Lin Y, Lin P, Zhao X, Cui L. Modulating extracellular matrix stiffness: a strategic approach to boost cancer immunotherapy. Cell Death & Disease. 2024;15(5):307.
56.Birnboim-Perach R, Benhar I. Using Combination therapy to overcome diverse challenges of Immune Checkpoint Inhibitors treatment. International journal of biological sciences. 2024;20(10):3911-22.
57.Hou J, Karin M, Sun B. Targeting cancer-promoting inflammation - have anti-inflammatory therapies come of age? Nature reviews Clinical oncology. 2021;18(5):261-79.
58.Stanilov N, Velikova T, Stanilova S. Navigating the Cytokine Seas: Targeting Cytokine Signaling Pathways in Cancer Therapy. International Journal of Molecular Sciences [Internet]. 2024; 25(2).
59.Wu B, Zhang B, Li B, Wu H, Jiang M. Cold and hot tumors: from molecular mechanisms to targeted therapy. Signal transduction and targeted therapy. 2024;9(1):274.
60.Almawash S. Revolutionary Cancer Therapy for Personalization and Improved Efficacy: Strategies to Overcome Resistance to Immune Checkpoint Inhibitor Therapy. Cancers. 2025;17(5).
61.Qu X, Tang Y, Hua S. Immunological Approaches Towards Cancer and Inflammation: A Cross Talk. 2018;Volume 9 - 2018.
62.Zhang A, Fan T, Liu Y, Yu G, Li C, Jiang Z. Regulatory T cells in immune checkpoint blockade antitumor therapy. Molecular Cancer. 2024;23(1):251.
63.Li C, Yu X, Han X, Lian C, Wang Z, Shao S, et al. Innate immune cells in tumor microenvironment: A new frontier in cancer immunotherapy. iScience. 2024;27(9):110750.
64.Zappavigna S, Cossu AM, Grimaldi A, Bocchetti M, Ferraro GA, Nicoletti GF, et al. Anti-Inflammatory Drugs as Anticancer Agents. Int J Mol Sci. 2020;21(7).
65.Shukla S, Shukla AK, Ray N, Upadhyay AM, Fahad FI, Dutta SD, et al. Targeting Pathways and Mechanisms in Gynecological Cancer with Antioxidant and Anti-Inflammatory Phytochemical Drugs. Onco [Internet]. 2025; 5(2).
66.Sarapultsev A, Gusev E, Komelkova M, Utepova I, Luo S, Hu D. JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions. Molecular biomedicine. 2023;4(1):40.
67.Imtiaz S, Ferdous UT, Nizela A, Hasan A, Shakoor A, Zia AW, et al. Mechanistic study of cancer drug delivery: Current techniques, limitations, and future prospects. European Journal of Medicinal Chemistry. 2025;290:117535.
68.Wang M, Chen S, He X, Yuan Y, Wei X. Targeting inflammation as cancer therapy. Journal of hematology & oncology. 2024;17(1):13.
69.Zhou X, Wu Y, Zhu Z, Lu C, Zhang C, Zeng L, et al. Mucosal immune response in biology, disease prevention and treatment. Signal transduction and targeted therapy. 2025;10(1):7.
70.Attiq A, Afzal S. Trinity of inflammation, innate immune cells and cross-talk of signalling pathways in tumour microenvironment. Frontiers in pharmacology. 2023;14:1255727.
71.Nigam M, Mishra AP, Deb VK, Dimri DB, Tiwari V, Bungau SG, et al. Evaluation of the association of chronic inflammation and cancer: Insights and implications. Biomedicine & Pharmacotherapy. 2023;164:115015.
72.Sandhbor P, John G, Bhat S, Goda JS. Immune response recalibration using immune therapy and biomimetic nano-therapy against high-grade gliomas and brain metastases. Asian Journal of Pharmaceutical Sciences. 2025;20(2):101021.
73.Passaro A, Al Bakir M, Hamilton EG, Diehn M, André F, Roy-Chowdhuri S, et al. Cancer biomarkers: Emerging trends and clinical implications for personalized treatment. Cell. 2024;187(7):1617-35.
74.Florescu DN, Boldeanu MV, Șerban RE, Florescu LM, Serbanescu MS, Ionescu M, et al. Correlation of the Pro-Inflammatory Cytokines IL-1β, IL-6, and TNF-α, Inflammatory Markers, and Tumor Markers with the Diagnosis and Prognosis of Colorectal Cancer. Life (Basel, Switzerland). 2023;13(12).
75.Das S, Dey MK, Devireddy R, Gartia MR. Biomarkers in Cancer Detection, Diagnosis, and Prognosis. Sensors [Internet]. 2024; 24(1).
76.Wang H, Zhang Y, Zhang H, Cao H, Mao J, Chen X, et al. Liquid biopsy for human cancer: cancer screening, monitoring, and treatment. MedComm. 2024;5(6):e564.
77.Wang S, Yang Y, Ma P, Huang H, Tang Q, Miao H, et al. Landscape and perspectives of macrophage -targeted cancer therapy in clinical trials. Molecular Therapy - Oncolytics. 2022;24:799-813.
78.Li R, Ye JJ, Gan L, Zhang M, Sun D, Li Y, et al. Traumatic inflammatory response: pathophysiological role and clinical value of cytokines. European journal of trauma and emergency surgery : official publication of the European Trauma Society. 2024;50(4):1313-30.
79.Ramos A, Sadeghi S, Tabatabaeian H. Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them. Int J Mol Sci. 2021;22(17).
80.Albini A, Di Paola L, Mei G, Baci D, Fusco N, Corso G, et al. Inflammation and cancer cell survival: TRAF2 as a key player. Cell Death Dis. 2025;16(1):292.
81.Shahgoli VK, Noorolyai S, Ahmadpour Youshanlui M, Saeidi H, Nasiri H, Mansoori B, et al. Inflammatory bowel disease, colitis, and cancer: unmasking the chronic inflammation link. International journal of colorectal disease. 2024;39(1):173.
82.Bhol NK, Bhanjadeo MM, Singh AK, Dash UC, Ojha RR, Majhi S, et al. The interplay between cytokines, inflammation, and antioxidants: mechanistic insights and therapeutic potentials of various antioxidants and anti-cytokine compounds. Biomedicine & Pharmacotherapy. 2024;178:117177.
83.Karimi S, Bakhshali R, Bolandi S, Zahed Z, Mojtaba Zadeh SS, Kaveh Zenjanab M, et al. For and against tumor microenvironment: Nanoparticle-based strategies for active cancer therapy. Materials Today Bio. 2025;31:101626.
84.Lu S, Li Y, Zhu C, Wang W, Zhou Y. Managing Cancer Drug Resistance from the Perspective of Inflammation. Journal of oncology. 2022;2022:3426407.
85.Giri S, Lamichhane G, Pandey J, Khadayat R, K. C S, Devkota HP, et al. Immune Modulation and Immunotherapy in Solid Tumors: Mechanisms of Resistance and Potential Therapeutic Strategies. International Journal of Molecular Sciences [Internet]. 2025; 26(7).
86.Zhao Y, Dong Q, Li J, Zhang K, Qin J, Zhao J, et al. Targeting cancer stem cells and their niche: perspectives for future therapeutic targets and strategies. Seminars in Cancer Biology. 2018;53:139-55.
87.Chu X, Tian W, Ning J, Xiao G, Zhou Y, Wang Z, et al. Cancer stem cells: advances in knowledge and implications for cancer therapy. Signal transduction and targeted therapy. 2024;9(1):170.
88.Sadiq IZ, Abubakar FS, Katsayal BS, Ibrahim B, Adamu A, Usman MA, et al. Stem cells in regenerative medicine: Unlocking therapeutic potential through stem cell therapy, 3D bioprinting, gene editing, and drug discovery. Biomedical Engineering Advances. 2025;9:100172.
89.Mikkili I, Suluvoy JK, Thathapudi JJ, Srirama K. Synergistic strategies for cancer treatment: leveraging natural products, drug repurposing and molecular targets for integrated therapy. Beni-Suef University Journal of Basic and Applied Sciences. 2024;13(1):96.
90.Pelly VS, Moeini A, Roelofsen LM, Bonavita E, Bell CR, Hutton C, et al. Anti-Inflammatory Drugs Remodel the Tumor Immune Environment to Enhance Immune Checkpoint Blockade Efficacy. Cancer discovery. 2021;11(10):2602-19.
91.Al Khzem AH, Gomaa MS, Alturki MS, Tawfeeq N, Sarafroz M, Alonaizi SM, et al. Drug Repurposing for Cancer Treatment: A Comprehensive Review. International Journal of Molecular Sciences [Internet]. 2024; 25(22).
 
Volume 10, Issue 39 - Serial Number 39
Original article
Autumn 2025
Pages 43-53

  • Receive Date 15 July 2025
  • Revise Date 25 September 2025
  • Accept Date 20 November 2025