Cancer-associated fibroblasts in triple-negative breast cancer: clinical transformation research progress_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HU Sichang , LI Na , CHEN Lijuan ,  DANG Zheng

Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Lanzhou 730050, P. R. China;

Corresponding?author：

DANG Zheng, Email: zaidongji@163.com

Keywords：

triple-negative breast cancer; cancer-associated fibroblasts; tumor microenvironment; immunotherapy

DOI：

10.7507/1007-9424.202508102

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize and review the clinical translational research progress of cancer-associated fibroblasts (CAFs) in triple-negative breast cancer (TNBC), aiming to provide new ideas for the treatment of TNBC. Method Relevant literature on studies of CAFs in TNBC in recent years was retrieved and reviewed. Results As the most important stromal cell component in the tumor microenvironment (TME), CAFs participate in tumor growth, invasion, immune suppression, and treatment resistance by secreting cytokines, chemokines, and remodeling the extracellular matrix. Based on this, the clinical translational strategies of CAFs in TNBC mainly include targeting CAFs markers and their oncogenic pathways, inhibiting or reversing the activation and recruitment of CAFs, and novel treatment methods such as photothermal therapy. Conclusions In the face of clinical treatment challenges such as drug-resistant TNBC, the research on CAFs provides new ideas for solving the complexity of the TME. Although targeting CAFs faces challenges due to their heterogeneity, it has been confirmed in current clinical research and trials that the combination of targeting CAFs with immunotherapy, chemotherapy, etc. is feasible, and it is expected to become a new treatment mode for TNBC.

1.	Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl), 2022, 135(5): 584-590.
2.	Denkert C, Liedtke C, Tutt A, et al. Molecular alterations in triple-negative breast cancer—the road to new treatment strategies. Lancet, 2017, 389(10087): 2430-2442.
3.	Harris MA, Savas P, Virassamy B, et al. Towards targeting the breast cancer immune microenvironment. Nat Rev Cancer, 2024, 24(8): 554-577.
4.	Abe K, Watabe T, Kaneda-Nakashima K, et al. Evaluation of targeted alpha therapy using [²¹¹At]FAPI1 in triple-negative breast cancer xenograft models. Int J Mol Sci, 2024, 25(21): 11567. doi: 10.3390/ijms252111567.
5.	Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med, 2021, 384(25): 2394-2405.
6.	Bianchini G, De Angelis C, Licata L, et al. Treatment landscape of triple-negative breast cancer—expanded options, evolving needs. Nat Rev Clin Oncol, 2022, 19(2): 91-113.
7.	Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med, 2013, 19(11): 1423-1437.
8.	Yang J, Xin B, Wang X, et al. Cancer-associated fibroblasts in breast cancer in the single-cell era: opportunities and challenges. Biochim Biophys Acta Rev Cancer, 2025, 1880(2): 189291. doi: 10.1016/j.bbcan.2025.189291.
9.	Sherman MH, Yu RT, Engle DD, et al. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell, 2014, 159(1): 80-93.
10.	Gao C, Jian C, Wang L, et al. FAP-targeting biomimetic nanosystem to restore the activated cancer-associated fibroblasts to quiescent state for breast cancer radiotherapy. Int J Pharm, 2025, 670: 125190. doi: 10.1016/j.ijpharm.2025.125190.
11.	Melero I, Tanos T, Bustamante M, et al. A first-in-human study of the fibroblast activation protein-targeted, 4-1BB agonist RO7122290 in patients with advanced solid tumors. Sci Transl Med, 2023, 15(695): eabp9229. doi: 10.1126/scitranslmed.abp9229.
12.	Zhang FF, Qiao Y, Xie Y, et al. Epitope-based minigene vaccine targeting fibroblast activation protein α induces specific immune responses and anti-tumor effects in 4T1 murine breast cancer model. Int Immunopharmacol, 2022, 112: 109237. doi: 10.1016/j.intimp.2022.109237.
13.	Das S, Valton J, Duchateau P, et al. Stromal depletion by TALEN-edited universal hypoimmunogenic FAP-CAR T cells enables infiltration and anti-tumor cytotoxicity of tumor antigen-targeted CAR-T immunotherapy. Front Immunol, 2023, 14: 1172681. doi: 10.3389/fimmu.2023.1172681.
14.	Garate-Soraluze E, Serrano-Mendioroz I, Fernández-Rubio L, et al. 4-1BB agonist targeted to fibroblast activation protein α synergizes with radiotherapy to treat murine breast tumor models. J Immunother Cancer, 2025, 13(2): e009852. doi: 10.1136/jitc-2024-009852.
15.	McGale J, Khurana S, Howell H, et al. FAP-targeted SPECT/CT and PET/CT imaging for breast cancer patients. Clin Nucl Med, 2025, 50(3): e138-e145. doi: 10.1097/RLU.0000000000005617.
16.	Chauhan VP, Martin JD, Liu H, et al. Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nat Commun, 2013, 4: 2516. doi: 10.1038/ncomms3516.
17.	Mei J, Chu J, Yang K, et al. Angiotensin receptor blocker attacks armored and cold tumors and boosts immune checkpoint blockade. J Immunother Cancer, 2024, 12(9): e009327. doi: 10.1136/jitc-2024-009327.
18.	Guan X, Shen Y, Zhao C, et al. Cascade-responsive nanoprodrug disrupts immune-fibroblast communications for potentiated cancer mechanoimmunotherapy. Adv Healthc Mater, 2025, 14(11): e2500176. doi: 10.1002/adhm.202500176.
19.	Su S, Chen J, Yao H, et al. CD10⁺GPR77⁺ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell, 2018, 172(4): 841-856.
20.	Fang J , Jiang Q , Yang X , et al. Construction of targeting GPR77⁺CD10⁺ lipid nanoparticles and validation of targeting capability in vitro and in vivo. Current Res Biotechnol, 2025, 9(000). doi: 10.1016/j.crbiot.2025.100291.
21.	Fan G, Yu B, Tang L, et al. TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer. Sci Transl Med, 2024, 16(741): eadj5705.
22.	Hu D, Li Z, Zheng B, et al. Cancer-associated fibroblasts in breast cancer: challenges and opportunities. Cancer Commun (Lond), 2022, 42(5): 401-434.
23.	Zhang H, Yue X, Chen Z, et al. Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials. Mol Cancer, 2023, 22(1): 159. doi: 10.1186/s12943-023-01860-5.
24.	Xu C, Zhao H, Chen H, et al. CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther, 2015, 9: 4953-4964.
25.	Ciavattone NG, Bevoor A, Farfel A, et al. Inhibiting CXCR4 reduces immunosuppressive effects of myeloid cells in breast cancer immunotherapy. Sci Rep, 2025, 15(1): 5204. doi: 10.1038/s41598-025-89882-5.
26.	Zhang Y, Han X, Wang K, et al. Co-delivery nanomicelles for potentiating TNBC immunotherapy by synergetically reshaping CAFs-mediated tumor stroma and reprogramming immunosuppressive microenvironment. Int J Nanomedicine, 2023, 18: 4329-4346.
27.	Bao G, Wang Z, Liu L, et al. Targeting CXCR4/CXCL12 axis via [¹⁷⁷Lu]Lu-DOTAGA. (SA. FAPi)₂ with CXCR4 antagonist in triple-negative breast cancer. Eur J Nucl Med Mol Imaging, 2024, 51(9): 2744-2757.
28.	Jang BY, Shin MK, Han DH, et al. Curcumin disrupts a positive feedback loop between ADMSCs and cancer cells in the breast tumor microenvironment via the CXCL12/CXCR4 axis. Pharmaceutics, 2023, 15(11): 2627. doi: 10.3390/pharmaceutics15112627.
29.	Wang Y, Zhao L, Han X, et al. Saikosaponin A inhibits triple-negative breast cancer growth and metastasis through downregulation of CXCR4. Front Oncol, 2020, 9: 1487. doi: 10.3389/fonc.2019.01487.
30.	Zhang P, Qin C, Liu N, et al. The programmed site-specific delivery of LY3200882 and PD-L1 siRNA boosts immunotherapy for triple-negative breast cancer by remodeling tumor microenvironment. Biomaterials, 2022 May: 284: 121518. doi: 10.1016/j.biomaterials.2022.121518.
31.	Yang M, Qin C, Tao L, et al. Synchronous targeted delivery of TGF-β siRNA to stromal and tumor cells elicits robust antitumor immunity against triple-negative breast cancer by comprehensively remodeling the tumor microenvironment. Biomaterials, 2023, 301: 122253. doi: 10.1016/j.biomaterials.2023.122253.
32.	Wu Y, Yi Z, Li J, et al. FGFR blockade boosts T cell infiltration into triple-negative breast cancer by regulating cancer-associated fibroblasts. Theranostics, 2022, 12(10): 4564-4580.
33.	Wang B, Liu W, Liu C, et al. Cancer-associated fibroblasts promote radioresistance of breast cancer cells via the HGF/c-Met signaling pathway. Int J Radiat Oncol Biol Phys, 2023, 116(3): 640-654.
34.	Osuala KO, Chalasani A, Aggarwal N, et al. Paracrine activation of STAT3 drives GM-CSF expression in breast carcinoma cells, generating a symbiotic signaling network with breast carcinoma-associated fibroblasts. Cancers (Basel), 2024, 16(16): 2910. doi: 10.3390/cancers16162910.
35.	Pernas S, Martin M, Kaufman PA, et al. Balixafortide plus eribulin in HER2-negative metastatic breast cancer: a phase 1, single-arm, dose-escalation trial. Lancet Oncol, 2018, 19(6): 812-824.
36.	Lai YW, Liu ZW, Lin MH, et al. Melatonin increases olaparib sensitivity and suppresses cancer-associated fibroblast infiltration via suppressing the LAMB3-CXCL2 axis in TNBC. Pharmacol Res, 2024, 209: 107429. doi: 10.1016/j.phrs.2024.107429.
37.	Xia J, Zhang S, Zhang R, et al. Targeting therapy and tumor microenvironment remodeling of triple-negative breast cancer by ginsenoside Rg3 based liposomes. J Nanobiotechnology, 2022, 20(1): 414. doi: 10.1186/s12951-022-01623-2.
38.	Xu S, Zheng S, Ma N, et al. Rhein potentiates doxorubicin in treating triple negative breast cancer by inhibiting cancer-associated fibroblasts. Biochem Pharmacol, 2024, 223: 116139. doi: 10.1016/j.bcp.2024.116139.
39.	Giannoni E, Bianchini F, Masieri L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res, 2010, 70(17): 6945-6956.
40.	Chen Y, McAndrews KM, Kalluri R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Rev Clin Oncol, 2021, 18(12): 792-804.
41.	Erez N, Truitt M, Olson P, et al. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell, 2010, 17(2): 135-147.
42.	Glabman RA, Choyke PL, Sato N. Cancer-associated fibroblasts: tumorigenicity and targeting for cancer therapy. Cancers (Basel), 2022, 14(16): 3906. doi: 10.3390/cancers14163906.
43.	Kojima Y, Acar A, Eaton EN, et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A, 2010, 107(46): 20009-20014.
44.	Toullec A, Gerald D, Despouy G, et al. Oxidative stress promotes myofibroblast differentiation and tumour spreading. EMBO Mol Med, 2010, 2(6): 211-230.
45.	De Luca G, Petrillo G, Scognamiglio I, et al. Fibroblasts activated by miRs-185-5p, miR-652-5p, and miR-1246 shape the tumor microenvironment in triple-negative breast cancer via PATZ1 downregulation. Cell Mol Life Sci, 2025, 82(1): 287. doi: 10.1007/s00018-025-05781-y.
46.	Quintavalle C, Ingenito F, Roscigno G, et al. Ex. 50. T aptamer impairs tumor-stroma cross-talk in breast cancer by targeting gremlin-1. Cell Death Discov, 2025, 11(1): 94. doi: 10.1038/s41420-025-02363-6.
47.	Cote GM, Tine BV, Clifton K, et al. First-in-class non-cellular targeting antibody-drug conjugate (ADC), micvotabart pelidotin (MICVO), in patients (PTS) with advanced sarcoma. ESMO Rare Cancers, 2025, 4: 100051. doi: 10.1016/j.esmorc.2025.100051.
48.	Rodriguez AB, Facklam A, Trickett J, et al. Mouse analog of micvotabart pelidotin sensitizes a refractory syngeneic breast cancer model to anti-PD1 therapy [abstract] // Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, 2025 Oct 22-26. Boston, MA. Philadelphia (PA): AACR. Mol Cancer Ther, 2025, 24(10 Suppl): Abstract nr A115. doi: org/10.1158/1535-7163.TARG-25-A115.
49.	Zhang Y, Zhou J, Wang Y, et al. Stimuli-responsive polymer-dasatinib prodrug to reprogram cancer-associated fibroblasts for boosted immunotherapy. J Control Release, 2025, 381: 113606. doi: 10.1016/j.jconrel.2025.113606.
50.	Desroys du Roure P, David T, Mallavialle A, et al. Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy. J Immunother Cancer, 2025, 13(1): e009548. doi: 10.1136/jitc-2024-009548.
51.	Tan Y, Yang YG, Zhang X, et al. Tumor cell-derived osteopontin promotes tumor fibrosis indirectly via tumor-associated macrophages. J Transl Med, 2025, 23(1): 432. doi: 10.1186/s12967-025-06444-z.
52.	Zhang Z, Wang Z, Xiong Y, et al. A two-pronged strategy to alleviate tumor hypoxia and potentiate photodynamic therapy by mild hyperthermia. Biomater Sci, 2022, 11(1): 108-118.
53.	Cao Y, Wen E, Chen Q, et al. Multifunctional ICG-SB@Lip-ZA Nanosystem focuses on remodeling the inflammatory-immunosuppressive microenvironment after photothermal therapy to potentiate cancer photothermal immunotherapy. Adv Healthc Mater, 2025, 14(1): e2402211. doi: 10.1002/adhm.202402211.
54.	Geng S, Xiang T, Shi Y, et al. Locally producing antibacterial peptide to deplete intratumoral pathogen for preventing metastatic breast cancer. Acta Pharm Sin B, 2025, 15(2): 1084-1097.
55.	Cords L, de Souza N, Bodenmiller B. Classifying cancer-associated fibroblasts—the good, the bad, and the target. Cancer Cell, 2024, 42(9): 1480-1485.

1. Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl), 2022, 135(5): 584-590.
2. Denkert C, Liedtke C, Tutt A, et al. Molecular alterations in triple-negative breast cancer—the road to new treatment strategies. Lancet, 2017, 389(10087): 2430-2442.
3. Harris MA, Savas P, Virassamy B, et al. Towards targeting the breast cancer immune microenvironment. Nat Rev Cancer, 2024, 24(8): 554-577.
4. Abe K, Watabe T, Kaneda-Nakashima K, et al. Evaluation of targeted alpha therapy using [²¹¹At]FAPI1 in triple-negative breast cancer xenograft models. Int J Mol Sci, 2024, 25(21): 11567. doi: 10.3390/ijms252111567.
5. Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med, 2021, 384(25): 2394-2405.
6. Bianchini G, De Angelis C, Licata L, et al. Treatment landscape of triple-negative breast cancer—expanded options, evolving needs. Nat Rev Clin Oncol, 2022, 19(2): 91-113.
7. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med, 2013, 19(11): 1423-1437.
8. Yang J, Xin B, Wang X, et al. Cancer-associated fibroblasts in breast cancer in the single-cell era: opportunities and challenges. Biochim Biophys Acta Rev Cancer, 2025, 1880(2): 189291. doi: 10.1016/j.bbcan.2025.189291.
9. Sherman MH, Yu RT, Engle DD, et al. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy. Cell, 2014, 159(1): 80-93.
10. Gao C, Jian C, Wang L, et al. FAP-targeting biomimetic nanosystem to restore the activated cancer-associated fibroblasts to quiescent state for breast cancer radiotherapy. Int J Pharm, 2025, 670: 125190. doi: 10.1016/j.ijpharm.2025.125190.
11. Melero I, Tanos T, Bustamante M, et al. A first-in-human study of the fibroblast activation protein-targeted, 4-1BB agonist RO7122290 in patients with advanced solid tumors. Sci Transl Med, 2023, 15(695): eabp9229. doi: 10.1126/scitranslmed.abp9229.
12. Zhang FF, Qiao Y, Xie Y, et al. Epitope-based minigene vaccine targeting fibroblast activation protein α induces specific immune responses and anti-tumor effects in 4T1 murine breast cancer model. Int Immunopharmacol, 2022, 112: 109237. doi: 10.1016/j.intimp.2022.109237.
13. Das S, Valton J, Duchateau P, et al. Stromal depletion by TALEN-edited universal hypoimmunogenic FAP-CAR T cells enables infiltration and anti-tumor cytotoxicity of tumor antigen-targeted CAR-T immunotherapy. Front Immunol, 2023, 14: 1172681. doi: 10.3389/fimmu.2023.1172681.
14. Garate-Soraluze E, Serrano-Mendioroz I, Fernández-Rubio L, et al. 4-1BB agonist targeted to fibroblast activation protein α synergizes with radiotherapy to treat murine breast tumor models. J Immunother Cancer, 2025, 13(2): e009852. doi: 10.1136/jitc-2024-009852.
15. McGale J, Khurana S, Howell H, et al. FAP-targeted SPECT/CT and PET/CT imaging for breast cancer patients. Clin Nucl Med, 2025, 50(3): e138-e145. doi: 10.1097/RLU.0000000000005617.
16. Chauhan VP, Martin JD, Liu H, et al. Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nat Commun, 2013, 4: 2516. doi: 10.1038/ncomms3516.
17. Mei J, Chu J, Yang K, et al. Angiotensin receptor blocker attacks armored and cold tumors and boosts immune checkpoint blockade. J Immunother Cancer, 2024, 12(9): e009327. doi: 10.1136/jitc-2024-009327.
18. Guan X, Shen Y, Zhao C, et al. Cascade-responsive nanoprodrug disrupts immune-fibroblast communications for potentiated cancer mechanoimmunotherapy. Adv Healthc Mater, 2025, 14(11): e2500176. doi: 10.1002/adhm.202500176.
19. Su S, Chen J, Yao H, et al. CD10⁺GPR77⁺ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell, 2018, 172(4): 841-856.
20. Fang J , Jiang Q , Yang X , et al. Construction of targeting GPR77⁺CD10⁺ lipid nanoparticles and validation of targeting capability in vitro and in vivo. Current Res Biotechnol, 2025, 9(000). doi: 10.1016/j.crbiot.2025.100291.
21. Fan G, Yu B, Tang L, et al. TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer. Sci Transl Med, 2024, 16(741): eadj5705.
22. Hu D, Li Z, Zheng B, et al. Cancer-associated fibroblasts in breast cancer: challenges and opportunities. Cancer Commun (Lond), 2022, 42(5): 401-434.
23. Zhang H, Yue X, Chen Z, et al. Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials. Mol Cancer, 2023, 22(1): 159. doi: 10.1186/s12943-023-01860-5.
24. Xu C, Zhao H, Chen H, et al. CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther, 2015, 9: 4953-4964.
25. Ciavattone NG, Bevoor A, Farfel A, et al. Inhibiting CXCR4 reduces immunosuppressive effects of myeloid cells in breast cancer immunotherapy. Sci Rep, 2025, 15(1): 5204. doi: 10.1038/s41598-025-89882-5.
26. Zhang Y, Han X, Wang K, et al. Co-delivery nanomicelles for potentiating TNBC immunotherapy by synergetically reshaping CAFs-mediated tumor stroma and reprogramming immunosuppressive microenvironment. Int J Nanomedicine, 2023, 18: 4329-4346.
27. Bao G, Wang Z, Liu L, et al. Targeting CXCR4/CXCL12 axis via [¹⁷⁷Lu]Lu-DOTAGA. (SA. FAPi)₂ with CXCR4 antagonist in triple-negative breast cancer. Eur J Nucl Med Mol Imaging, 2024, 51(9): 2744-2757.
28. Jang BY, Shin MK, Han DH, et al. Curcumin disrupts a positive feedback loop between ADMSCs and cancer cells in the breast tumor microenvironment via the CXCL12/CXCR4 axis. Pharmaceutics, 2023, 15(11): 2627. doi: 10.3390/pharmaceutics15112627.
29. Wang Y, Zhao L, Han X, et al. Saikosaponin A inhibits triple-negative breast cancer growth and metastasis through downregulation of CXCR4. Front Oncol, 2020, 9: 1487. doi: 10.3389/fonc.2019.01487.
30. Zhang P, Qin C, Liu N, et al. The programmed site-specific delivery of LY3200882 and PD-L1 siRNA boosts immunotherapy for triple-negative breast cancer by remodeling tumor microenvironment. Biomaterials, 2022 May: 284: 121518. doi: 10.1016/j.biomaterials.2022.121518.
31. Yang M, Qin C, Tao L, et al. Synchronous targeted delivery of TGF-β siRNA to stromal and tumor cells elicits robust antitumor immunity against triple-negative breast cancer by comprehensively remodeling the tumor microenvironment. Biomaterials, 2023, 301: 122253. doi: 10.1016/j.biomaterials.2023.122253.
32. Wu Y, Yi Z, Li J, et al. FGFR blockade boosts T cell infiltration into triple-negative breast cancer by regulating cancer-associated fibroblasts. Theranostics, 2022, 12(10): 4564-4580.
33. Wang B, Liu W, Liu C, et al. Cancer-associated fibroblasts promote radioresistance of breast cancer cells via the HGF/c-Met signaling pathway. Int J Radiat Oncol Biol Phys, 2023, 116(3): 640-654.
34. Osuala KO, Chalasani A, Aggarwal N, et al. Paracrine activation of STAT3 drives GM-CSF expression in breast carcinoma cells, generating a symbiotic signaling network with breast carcinoma-associated fibroblasts. Cancers (Basel), 2024, 16(16): 2910. doi: 10.3390/cancers16162910.
35. Pernas S, Martin M, Kaufman PA, et al. Balixafortide plus eribulin in HER2-negative metastatic breast cancer: a phase 1, single-arm, dose-escalation trial. Lancet Oncol, 2018, 19(6): 812-824.
36. Lai YW, Liu ZW, Lin MH, et al. Melatonin increases olaparib sensitivity and suppresses cancer-associated fibroblast infiltration via suppressing the LAMB3-CXCL2 axis in TNBC. Pharmacol Res, 2024, 209: 107429. doi: 10.1016/j.phrs.2024.107429.
37. Xia J, Zhang S, Zhang R, et al. Targeting therapy and tumor microenvironment remodeling of triple-negative breast cancer by ginsenoside Rg3 based liposomes. J Nanobiotechnology, 2022, 20(1): 414. doi: 10.1186/s12951-022-01623-2.
38. Xu S, Zheng S, Ma N, et al. Rhein potentiates doxorubicin in treating triple negative breast cancer by inhibiting cancer-associated fibroblasts. Biochem Pharmacol, 2024, 223: 116139. doi: 10.1016/j.bcp.2024.116139.
39. Giannoni E, Bianchini F, Masieri L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res, 2010, 70(17): 6945-6956.
40. Chen Y, McAndrews KM, Kalluri R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Rev Clin Oncol, 2021, 18(12): 792-804.
41. Erez N, Truitt M, Olson P, et al. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell, 2010, 17(2): 135-147.
42. Glabman RA, Choyke PL, Sato N. Cancer-associated fibroblasts: tumorigenicity and targeting for cancer therapy. Cancers (Basel), 2022, 14(16): 3906. doi: 10.3390/cancers14163906.
43. Kojima Y, Acar A, Eaton EN, et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A, 2010, 107(46): 20009-20014.
44. Toullec A, Gerald D, Despouy G, et al. Oxidative stress promotes myofibroblast differentiation and tumour spreading. EMBO Mol Med, 2010, 2(6): 211-230.
45. De Luca G, Petrillo G, Scognamiglio I, et al. Fibroblasts activated by miRs-185-5p, miR-652-5p, and miR-1246 shape the tumor microenvironment in triple-negative breast cancer via PATZ1 downregulation. Cell Mol Life Sci, 2025, 82(1): 287. doi: 10.1007/s00018-025-05781-y.
46. Quintavalle C, Ingenito F, Roscigno G, et al. Ex. 50. T aptamer impairs tumor-stroma cross-talk in breast cancer by targeting gremlin-1. Cell Death Discov, 2025, 11(1): 94. doi: 10.1038/s41420-025-02363-6.
47. Cote GM, Tine BV, Clifton K, et al. First-in-class non-cellular targeting antibody-drug conjugate (ADC), micvotabart pelidotin (MICVO), in patients (PTS) with advanced sarcoma. ESMO Rare Cancers, 2025, 4: 100051. doi: 10.1016/j.esmorc.2025.100051.
48. Rodriguez AB, Facklam A, Trickett J, et al. Mouse analog of micvotabart pelidotin sensitizes a refractory syngeneic breast cancer model to anti-PD1 therapy [abstract] // Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, 2025 Oct 22-26. Boston, MA. Philadelphia (PA): AACR. Mol Cancer Ther, 2025, 24(10 Suppl): Abstract nr A115. doi: org/10.1158/1535-7163.TARG-25-A115.
49. Zhang Y, Zhou J, Wang Y, et al. Stimuli-responsive polymer-dasatinib prodrug to reprogram cancer-associated fibroblasts for boosted immunotherapy. J Control Release, 2025, 381: 113606. doi: 10.1016/j.jconrel.2025.113606.
50. Desroys du Roure P, David T, Mallavialle A, et al. Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy. J Immunother Cancer, 2025, 13(1): e009548. doi: 10.1136/jitc-2024-009548.
51. Tan Y, Yang YG, Zhang X, et al. Tumor cell-derived osteopontin promotes tumor fibrosis indirectly via tumor-associated macrophages. J Transl Med, 2025, 23(1): 432. doi: 10.1186/s12967-025-06444-z.
52. Zhang Z, Wang Z, Xiong Y, et al. A two-pronged strategy to alleviate tumor hypoxia and potentiate photodynamic therapy by mild hyperthermia. Biomater Sci, 2022, 11(1): 108-118.
53. Cao Y, Wen E, Chen Q, et al. Multifunctional ICG-SB@Lip-ZA Nanosystem focuses on remodeling the inflammatory-immunosuppressive microenvironment after photothermal therapy to potentiate cancer photothermal immunotherapy. Adv Healthc Mater, 2025, 14(1): e2402211. doi: 10.1002/adhm.202402211.
54. Geng S, Xiang T, Shi Y, et al. Locally producing antibacterial peptide to deplete intratumoral pathogen for preventing metastatic breast cancer. Acta Pharm Sin B, 2025, 15(2): 1084-1097.
55. Cords L, de Souza N, Bodenmiller B. Classifying cancer-associated fibroblasts—the good, the bad, and the target. Cancer Cell, 2024, 42(9): 1480-1485.

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