Exploring Recent Advancements in Nanomedicine for Tumor Microenvironmental Tissue Engineering

Year : 2025 | Volume : 16 | 03 | Page :
    By

    Sudhamani T,

  • Jananipriya K,

  • Dhanasekar J,

  • Selvakumar M,

  • Nandhakumaran S,

  • Lathamani L,

  1. Professor, Department of Pharmaceutics, Vivekanandha Pharmacy College for Women, Sankari, Tamil Nadu, India
  2. Professor, Department of Pharmaceutics, Vivekanandha Pharmacy College for Women, Sankari, Tamil Nadu, India
  3. Professor, Department of Pharmaceutics, Vivekanandha Pharmacy College for Women, Sankari, Tamil Nadu, India
  4. Professor, Department of Pharmaceutics, Vivekanandha Pharmacy College for Women, Sankari, Tamil Nadu, India
  5. Professor, Department of Pharmaceutics, Vivekanandha Pharmacy College for Women, Sankari, Tamil Nadu, India
  6. Professor, Department of Pharmaceutics, Vivekanandha Pharmacy College for Women, Sankari, Tamil Nadu, India

Abstract

The combination of tissue engineering and nanomedicine is transforming cancer treatment by offering creative ways to get around problems with conventional therapies. Recent developments in nanomedicine are examined in this review, with an emphasis on how they might be used to comprehend and control the tumor microenvironment (TME), a dynamic and complex environment that has a major impact on the course of cancer and the effectiveness of treatment. Targeted interactions inside the TME are made possible by emerging nanotechnologies that provide regulated release mechanisms, real-time monitoring, and precise drug administration. At the same time, tissue engineering techniques have proved crucial in developing physiologically appropriate 3D tumor models that more closely resemble in vivo circumstances than conventional 2D cultures. Deeper understanding of tumor biology, angiogenesis, immunological evasion, and treatment resistance is made possible by these engineered models. Recent advancements in stimuli-responsive nanoparticles, organ-on-chip platforms, and biomaterials have improved the ability to study and modify the TME for therapeutic advantage. When taken as a whole, these multidisciplinary developments have enormous potential for creating more potent, patient-specific cancer treatments as well as enhancing drug screening and disease modeling systems. This study emphasizes how tissue engineering and nanomedicine work together to revolutionize personalized medicine and cancer research.

Keywords: Nanomedicine, tumour microenvironment, tissue engineering ,tumor microenvironment, cancer-associated fibroblasts.

How to cite this article:
Sudhamani T, Jananipriya K, Dhanasekar J, Selvakumar M, Nandhakumaran S, Lathamani L. Exploring Recent Advancements in Nanomedicine for Tumor Microenvironmental Tissue Engineering. Research and Reviews: A Journal of Pharmaceutical Science. 2025; 16(03):-.
How to cite this URL:
Sudhamani T, Jananipriya K, Dhanasekar J, Selvakumar M, Nandhakumaran S, Lathamani L. Exploring Recent Advancements in Nanomedicine for Tumor Microenvironmental Tissue Engineering. Research and Reviews: A Journal of Pharmaceutical Science. 2025; 16(03):-. Available from: https://journals.stmjournals.com/rrjops/article=2025/view=228476


References

1. Lee S, Kim G, Lee J, Lee AC, Kwon S. Mapping cancer biology in space: applications and perspectives on spatial omics for oncology. Mol Cancer. 2024;23(1). doi:10.1186/s12943-024-01941-z.
2. Ungefroren H, Seidl D, Sebens S, Hass R, Lehnert H. Interaction of tumor cells with the microenvironment. Cell Commun Signal. 2011;9(1):18. doi:10.1186/1478-811X-9-18.
3. Ma H, Qin J, Xu H. Biomimetic tumor microenvironment on a microfluidic platform. Biomicrofluidics. 2013;7(1):011501. doi:10.1063/1.4774070.
4. Dzobo K. Taking a full snapshot of cancer biology: deciphering the tumor microenvironment for effective cancer therapy in the oncology clinic. OMICS. 2020;24(4):175–9. doi:10.1089/omi.2020.0019.
5. Guller AE, Zvyagin AV, Grebenyuk PN, Deyev SM, Shekhter AB. Bioreactor-based tumor tissue engineering. Acta Naturae. 2016;8(3):44–58. doi:10.32607/20758251-2016-8-3-44-58.
6. Son B, Lee S, Youn H, Kim E, Kim W, Youn B. The role of tumor microenvironment in therapeutic resistance. Oncotarget. 2016;8(3):3933–45. doi:10.18632/oncotarget.13907.
7. Zhang Q, Sun S, Lou Y, Ji Y, Jin R, Chen Z, et al. Cancer associated fibroblasts under therapy induced senescence in the tumor microenvironment (Review). Exp Ther Med. 2024;27(4). doi:10.3892/etm.2024.12438.
8. Wu T, Dai Y. Tumor microenvironment and therapeutic response. Cancer Lett. 2017;387:61–8. doi:10.1016/j.canlet.2016.01.043.
9. Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci. 2018;25(1):20. doi:10.1186/s12929-018-0426-4.
10. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009;19(2):156–72. doi:10.1038/cr.2009.5.
11. Dai X, Guo X, Liu J, Cheng A, Peng X, Jia R, et al. Circular RNA circGRAMD1B inhibits gastric cancer progression by sponging miR-130a-3p and regulating PTEN and p21 expression. Aging. 2019;11(23):9689–708. doi:10.18632/aging.102415.
12. Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18(2):99–115. doi:10.1038/s41573-018-0004-1.
13. Ramamonjisoa N, Ackerstaff E. Characterization of the tumor microenvironment and tumor–stromal interactions by non-invasive preclinical imaging. Front Oncol. 2017;7:3. doi:10.3389/fonc.2017.00003.
14. Maishi N, Hida K. Tumor endothelial cells accelerate tumor metastasis. Cancer Sci. 2017;108(10):1921–6. doi:10.1111/cas.13336.
15. Watanabe K, Panchy N, Noguchi S, Suzuki H, Hong T. Combinatorial perturbation analysis reveals divergent regulations of mesenchymal genes during epithelial-to-mesenchymal transition. NPJ Syst Biol Appl. 2019;5(1). doi:10.1038/s41540-019-0091-9.
16. Li H, Courtois ET, Sengupta D, Tan Y, Chen KH, Goh JJL, et al. Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors. Nat Genet. 2017;49(5):708–18. doi:10.1038/ng.3818.
17. Lee SY, Jeong EK, Jeon HM, Kim CH. Implications of epithelial-mesenchymal transition in cancer stem cells: therapeutic targets and clinical relevance. Expert Rev Mol Sci. 2014;16(3):289–300. doi:10.1586/14737175.2014.884927.
18. Talukdar S, Bhoopathi P, Emdad L, Das S, Sarkar D, Fisher PB. Dormancy and cancer stem cells: an enigma for cancer therapeutic targeting. Adv Cancer Res. 2019;141:43–84. doi:10.1016/bs.acr.2018.11.002.
19. Butti R, Gunasekaran VP, Kumar TVS, Banerjee P, Kundu GC. Breast cancer stem cells: biology and therapeutic implications. Int J Biochem Cell Biol. 2019;107:38–52. doi:10.1016/j.biocel.2018.12.001.
20. Batlle E, Clevers H. Cancer stem cells revisited. Nat Med. 2017;23(10):1124–34. doi:10.1038/nm.4409.
21. Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell. 2014;14(3):275–91. doi:10.1016/j.stem.2014.02.006.
22. Najafi M, Mortezaee K, Majidpoor J. Cancer stem cell (CSC) resistance drivers. Life Sci. 2019;234:116781. doi:10.1016/j.lfs.2019.116781.
23. Fontana F, Carollo E, Melling GE, Carter DRF. Extracellular vesicles: emerging modulators of cancer drug resistance. Cancers. 2021;13(4):749. doi:10.3390/cancers13040749.
24. Vasconcelos MH, Caires HR, Ābols A, Xavier CPR, Linē A. Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance. Drug Resist Updat. 2019;47:100647. doi:10.1016/j.drup.2019.100647.
25. Camorani S, Hill BS, Fontanella R, Greco A, Gramanzini M, Auletta L, et al. Inhibition of bone marrow-derived mesenchymal stem cells homing towards triple-negative breast cancer microenvironment using an anti-PDGFRβ aptamer. Theranostics. 2017;7(15):3595–607. doi:10.7150/thno.20481.
26. Nandy SB, Arumugam A, Subramani R, Pedroza D, Hernandez K, Saltzstein E, et al. MicroRNA-125a influences breast cancer stem cells by targeting leukemia inhibitory factor receptor which regulates the Hippo signaling pathway. Oncotarget. 2015;6(19):17366–78. doi:10.18632/oncotarget.4020.
27. O’Conor CJ, Chen T, González I, Cao D, Peng Y. Cancer stem cells in triple-negative breast cancer: a potential target and prognostic marker. Biomark Med. 2018;12(7):813–20. doi:10.2217/bmm-2017-0398.
28. McDermott SP, Wicha MS. Targeting breast cancer stem cells. Mol Oncol. 2010;4(5):404–19. doi:10.1016/j.molonc.2010.06.005.
29. Azzam DJ, Zhao D, Sun J, Minn AJ, Ranganathan P, Drews-Elger K, et al. Triple negative breast cancer initiating cell subsets differ in functional and molecular characteristics and in γ-secretase inhibitor drug responses. EMBO Mol Med. 2013;5(10):1502–22. doi:10.1002/emmm.201302558.
30. Lindner U, Kramer J, Behrends J, Driller B, Wendler NO, Boehrnsen F, et al. Improved proliferation and differentiation capacity of human mesenchymal stromal cells cultured with basement-membrane extracellular matrix proteins. Cytotherapy. 2010;12(8):992–1005. doi:10.3109/14653249.2010.501791.
31. Keller PJ, Arendt LM, Skibinski A, Logvinenko T, Klebba I, Dong S, et al. Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci U S A. 2012;109(8):2772–7. doi:10.1073/pnas.1017626108.
32. Ye J, Wu D, Wu P, Chen Z, Huang J. The cancer stem cell niche: cross talk between cancer stem cells and their microenvironment. Tumour Biol. 2014;35(5):3945–51. doi:10.1007/s13277-013-1561-x.
33. Bussard KM, Mutkus L, Stumpf K, Gomez-Manzano C, Marini FC. Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res. 2016;18(1):84. doi:10.1186/s13058-016-0740-2.
34. Su S, Chen J, Yao H, Liu J, Yu S, Lao L, et al. CD10+GPR77+ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell. 2018;172(4):841–56.e16. doi:10.1016/j.cell.2018.01.009.
35. Koliaraki V, Pallangyo CK, Greten FR, Kollias G. Mesenchymal cells in colon cancer. Gastroenterology. 2017;152(5):964–79. doi:10.1053/j.gastro.2016.11.049.
36. Tao L, Huang G, Song H, Chen Y, Chen L. Cancer associated fibroblasts: an essential role in the tumor microenvironment. Oncol Lett. 2017;14(3):2611–20. doi:10.3892/ol.2017.6497.
37. Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev. 2016;30(9):1002–19. doi:10.1101/gad.279737.116.
38. Wang X, Sun W, Shen W, Xia M, Chen C, Xiang D, et al. Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis. J Hepatol. 2016;64(6):1283–94. doi:10.1016/j.jhep.2016.01.019.
39. Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takashi S, et al. Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell. 2011;19(2):257–72. doi:10.1016/j.ccr.2011.01.020.
40. Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582–98. doi:10.1038/nrc.2016.73.
41. Wang Z, Xu Q, Zhang N, Du X, Xu G, Yan X, et al. FAP promotes immunosuppression by cancer-associated fibroblasts in the tumor microenvironment via STAT3-CCL2 signaling. Cancer Res. 2022;82(6):1630–44. doi:10.1158/0008-5472.CAN-21-1305.
42. Malfitano AM, Pisanti S, Napolitano F, Di Somma S, Martinelli R, Portella G. Tumor-associated macrophage status in cancer treatment. Cancers. 2020;12(7):1987. doi:10.3390/cancers12071987.
43. Pan Y, Yu Y, Wang X, Zhang T. Tumor-associated macrophages in tumor immunity. Front Immunol. 2020;11:583084. doi:10.3389/fimmu.2020.583084.
44. Komohara Y, Fujiwara Y, Ohnishi K, Takeya M. Tumor-associated macrophages: potential therapeutic targets for anti-cancer therapy. Adv Drug Deliv Rev. 2016;99(Pt B):180–5. doi:10.1016/j.addr.2015.11.009.
45. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014;41(1):49–61. doi:10.1016/j.immuni.2014.06.010.
46. Riabov V, Gudima A, Wang N, Mickley A, Orekhov A, Kzhyshkowska J. Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol. 2014;5:75. doi:10.3389/fphys.2014.00075.
47. Mantovani A, Allavena P. The interaction of anticancer therapies with tumor-associated macrophages. J Exp Med. 2015;212(4):435–45. doi:10.1084/jem.20150295.
48. Genin M, Clement F, Fattaccioli A, Raes M, Michiels C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer. 2015;15:577. doi:10.1186/s12885-015-1546-9.
49. Pathria P, Louis TL, Varner JA. Targeting tumor-associated macrophages in cancer. Trends Immunol. 2019;40(4):310–27. doi:10.1016/j.it.2019.02.003.
50. Chanmee T, Ontong P, Konno K, Itano N. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers. 2014;6(3):1670–90. doi:10.3390/cancers6031670.
51. He Z, Ding J, Huie M, Yang Y, Zhang Y. Role of tumor-associated macrophages in the development of gastrointestinal tumors. Biochim Biophys Acta Rev Cancer. 2021;1876(2):188616. doi:10.1016/j.bbcan.2021.188616.
52. Jang J, Kim J, Lee K, Kim C. Tumor-associated macrophage as a prognostic biomarker of non-small cell lung cancer: a meta-analysis. Sci Rep. 2020;10(1):15203. doi:10.1038/s41598-020-72181-w.
53. Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8(8):618–31. doi:10.1038/nrc2444.
54. Lin EY, Pollard JW. Tumor-associated macrophages press the angiogenic switch in breast cancer. Cancer Res. 2007;67(11):5064–6. doi:10.1158/0008-5472.CAN-07-0912.
55. Hussain M, Adah D, Tariq M, Lu Y, Zhang J, Liu J. CXCL13/CXCR5 signaling axis in cancer. Life Sci. 2019;227:175–86. doi:10.1016/j.lfs.2019.04.053.
56. Wang L, Zhu B, Zhang M, Wang X. Roles of CCL3 in tumor microenvironment. Cancer Manag Res. 2020;12:6163–72. doi:10.2147/CMAR.S258237.
57. Shree T, Olson OC, Elie BT, Kester JC, Garfall AL, Simpson K, et al. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev. 2011;25(23):2465–79. doi:10.1101/gad.180331.111.
58. Bonapace L, Coissieux MM, Wyckoff J, Mertz KD, Varga Z, Junt T, et al. Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature. 2014;515(7525):130–3. doi:10.1038/nature13862.
59. Qiu SQ, Waaijer SJH, Zwager MC, de Vries EGE, van der Vegt B, Schröder CP. Tumor-associated macrophages in breast cancer: innocent bystander or important player? Cancer Treat Rev. 2018;70:178–89. doi:10.1016/j.ctrv.2018.08.010.
60. Ruffell B, Coussens LM. Macrophages and therapeutic resistance in cancer. Cancer Cell. 2015;27(4):462–72. doi:10.1016/j.ccell.2015.02.015.
61. Goswami KK, Ghosh T, Ghosh S, Sarkar M, Bose A, Baral R. Tumor promoting role of anti-tumor macrophages in tumor microenvironment. Cell Immunol. 2017; 316:1–10. doi:10.1016/j.cellimm.2017.04.005.
62. Cassetta L, Pollard JW. Targeting macrophages: therapeutic approaches in cancer. Nat Rev Drug Discov. 2018;17(12):887–904. doi:10.1038/nrd.2018.169.
63. Zhou J, Tang Z, Gao S, Li C, Feng Y, Zhou X. Tumor-associated macrophages: recent insights and therapies. Front Oncol. 2020;10:188. doi:10.3389/fonc.2020.00188.
64. Ovais M, Guo M, Chen C. Tailoring nanomaterials for targeting tumor-associated macrophages. Adv Mater. 2019;31(19):1808303. doi:10.1002/adma.201808303.
65. Ramesh A, Brouillard A, Kumar S, Nandi D, Kulkarni A. Dual inhibition of CSF1R and MAPK pathways using supramolecular nanoparticles enhances macrophage immunotherapy. Biomaterials. 2020;227:119559. doi:10.1016/j.biomaterials.2019.119559.
66. Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017;14(7):399–416. doi:10.1038/nrclinonc.2016.217.
67. Guerriero JL. Macrophages: their untold story in T cell activation and function. Int Rev Cell Mol Biol. 2019;342:73–93. doi:10.1016/bs.ircmb.2018.07.001.
68. Xu J, Escamilla J, Mok S, David J, Priceman S, West B, et al. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer. Cancer Res. 2013;73(9):2782–94. doi:10.1158/0008-5472.CAN-12-3981.
69. Strachan DC, Ruffell B, Oei Y, Bissell MJ, Coussens LM, Pryer N, et al. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. Oncoimmunology. 2013;2(12):e26968. doi:10.4161/onci.26968.
70. Holmgaard RB, Zamarin D, Lesokhin A, Merghoub T, Wolchok JD. Targeting myeloid-derived suppressor cells with colony stimulating factor-1 receptor blockade can reverse immune resistance to immunotherapy in indoleamine 2,3-dioxygenase-expressing tumors. EBioMedicine. 2016;6:50–8. doi:10.1016/j.ebiom.2016.02.024.
71. Papadopoulos KP, Gluck L, Martin LP, Olszanski AJ, Tolcher AW, Ngarmchamnanrith G, et al. First-in-human study of AMG 820, a monoclonal anti-colony-stimulating factor 1 receptor antibody, in patients with advanced solid tumors. Clin Cancer Res. 2017;23(19):5703–10. doi:10.1158/1078-0432.CCR-16-3223.
72. von Tresckow B, Morschhauser F, Ribrag V, Topp MS, Chien C, Seetharam S, et al. An open-label, multicenter, phase I/II study of JNJ-40346527, a CSF-1R inhibitor, in patients with relapsed or refractory Hodgkin lymphoma. Clin Cancer Res. 2015;21(8):1843–50. doi:10.1158/1078-0432.CCR-14-1845.
73. Gomez-Roca CA, Italiano A, Le Tourneau C, Cassier PA, Toulmonde M, D’Angelo SP, et al. Phase I study of emactuzumab single agent in patients with locally advanced or metastatic solid tumors. Clin Cancer Res. 2019;25(17):5468–77. doi:10.1158/1078-0432.CCR-18-4123.
74. Cassier PA, Italiano A, Gomez-Roca CA, Le Tourneau C, Toulmonde M, Cannarile MA, et al. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 2015;16(8):949–56. doi:10.1016/S1470-2045(15)00132-1.
75. Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25(6):846–59. doi:10.1016/j.ccr.2014.05.016.
76. Kumar V, Donthireddy L, Marvel D, Condamine T, Wang F, Lavilla-Alonso S, et al. Cancer-associated fibroblasts neutralize the anti-tumor effect of CSF1 receptor blockade by inducing PMN-MDSC infiltration of tumors. Cancer Cell. 2017;32(5):654–68.e5. doi:10.1016/j.ccell.2017.10.005.
77. Dammeijer F, van Gulijk M, Mulder EE, Lukkes M, Klaase L, van den Bosch T, et al. The PD-1/PD-L1-checkpoint restrains T cell immunity in tumor-draining lymph nodes. Cancer Cell. 2020;38(5):685–700.e8. doi:10.1016/j.ccell.2020.09.001.
78. Peranzoni E, Lemoine J, Vimeux L, Feuillet V, Barrin S, Kantari-Mimoun C, et al. Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti–PD-1 treatment. Proc Natl Acad Sci U S A. 2018;115(17):E4041–50. doi:10.1073/pnas.1720948115.
79. Pathria P, Louis TL, Varner JA. Targeting tumor-associated macrophages in cancer. Trends Immunol. 2019;40(4):310–27. doi:10.1016/j.it.2019.02.003.
80. Li C, Xu X, Wei S, Jiang P, Xue L, Wang J, et al. Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer. J Immunother Cancer. 2021;9(1):e001341. doi:10.1136/jitc-2020-001341.
81. Jeong H, Kim S, Hong BJ, Lee CJ, Kim YE, Bok S, et al. Tumor-associated macrophages enhance tumor hypoxia and aerobic glycolysis. Cancer Res. 2019;79(4):795–806. doi:10.1158/0008-5472.CAN-18-2545.
82. Zhang Y, Cheng S, Zhang M, Zhen L, Pang D, Zhang Q, et al. High-infiltration of tumor-associated macrophages predicts unfavorable clinical outcome for node-negative breast cancer. PLoS One. 2013;8(9):e76147. doi:10.1371/journal.pone.0076147.
83. Goossens P, Rodriguez-Vita J, Etzerodt A, Masse M, Rastoin O, Gouirand V, et al. Membrane cholesterol efflux drives tumor-associated macrophage reprogramming and tumor progression. Cell Metab. 2019;29(6):1376–89.e4. doi:10.1016/j.cmet.2019.02.016.
84. Zhang J, Xu J, Zhang R, Sen A, Sun X, Chen J, et al. Pyruvate dehydrogenase kinase-mediated glycolytic metabolism promotes PD-L1 expression in tumor-associated macrophages. Front Immunol. 2022;13: 865940. doi:10.3389/fimmu.2022.865940.
85. Colegio OR, Chu NQ, Szabo AL, Chu T, Rhebergen AM, Jairam V, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature. 2014;513(7519):559–63. doi:10.1038/nature13490.
86. Mu X, Shi W, Xu Y, Xu C, Zhao T, Geng B, et al. Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/STAT3 signaling pathway in breast cancer. Cell Cycle. 2018;17(4):428–38. doi:10.1080/15384101.2018.1444305.
87. Penny HL, Sieow JL, Adriani G, Yeap WH, See Chi Ee P, San Luis B, et al. Warburg metabolism in tumor-conditioned macrophages promotes metastasis in human pancreatic ductal adenocarcinoma. Oncoimmunology. 2016;5(8):e1191731. doi:10.1080/2162402X.2016.1191731.
88. Zhao Y, Guo S, Deng J, Shen J, Du F, Wu X, et al. VEGF drives cancer-initiating stem cells through VEGFR-2/Stat3 signaling to upregulate Myc and Sox2. Oncogene. 2015;34(24):3107–19. doi:10.1038/onc.2014.257.
89. Vitale I, Manic G, Coussens LM, Kroemer G, Galluzzi L. Macrophages and metabolism in the tumor microenvironment. Cell Metab. 2019;30(1):36–50. doi:10.1016/j.cmet.2019.06.001.
90. Singh Y, Pawar VK, Meher JG, Raval K, Kumar A, Shrivastava R, et al. Targeting tumor associated macrophages (TAMs) via nanocarriers. J Control Release. 2017;254:92–106. doi:10.1016/j.jconrel.2017.03.395.
91. Poh AR, Ernst M. Targeting macrophages in cancer: from bench to bedside. Front Oncol. 2018;8:49. doi:10.3389/fonc.2018.00049.
92. Genard G, Lucas S, Michiels C. Reprogramming of tumor-associated macrophages with anticancer therapies: radiotherapy versus chemo- and immunotherapies. Front Immunol. 2017;8:828. doi:10.3389/fimmu.2017.00828.

Ahead of Print Subscription Review Article
Volume 16
03
Received 18/09/2025
Accepted 29/09/2025
Published 01/10/2025
Publication Time 13 Days
54


My IP

PlumX Metrics