G. Bianchini, C. De Angelis, L. Licata, L. Gianni, Treatment landscape of triple-negative breast cancer - expanded options, evolving needs. Nat. Reviews Clin. Oncol. 19, 91–113 (2022)
R.A. Leon-Ferre, M.P. Goetz, Advances in systemic therapies for triple negative breast cancer. Bmj-Brit Med. J. 381, (2023)
M.A. Harris, P. Savas, B. Virassamy, M.M.R. O’Malley, J. Kay, S.N. Mueller, L.K. Mackay, R. Salgado, S. Loi, Towards targeting the breast cancer immune microenvironment. Nat. Rev. Cancer. 24, 554–577 (2024)
Article CAS PubMed Google Scholar
H. Sabit, A. Adel, M.M. Abdelfattah, R.M. Ramadan, M. Nazih, S. Abdel-Ghany, A. El-hashash, B. Arneth, The role of tumor microenvironment and immune cell crosstalk in triple-negative breast cancer (TNBC): Emerging therapeutic opportunities. Cancer Lett. 628, (2025)
B. Wilczynski, A. Dabrowska, J. Kulbacka, D. Baczynska, Chemoresistance and the tumor microenvironment: the critical role of cell-cell communication. Cell. Communication Signal. 22, (2024)
A. Mousset, E. Lecorgne, I. Bourget, P. Lopez, K. Jenovai, J. Cherfils-Vicini, C. Dominici, G. Rios, C. Girard-Riboulleau, B.D. Liu, D.L. Spector, S. Ehmsen, S. Renault, C. Hego, F. Mechta-Grigoriou, F.C. Bidard, M.G. Terp, M. Egeblad, C. Gaggioli, J. Albrengues, Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation. Cancer cell. 41, 757– (2023)
Article CAS PubMed PubMed Central Google Scholar
L.Y. Lao, W.F. Zeng, P.H. Huang, H.P. Chen, Z.S. Jia, P. Wang, D. Huang, J.N. Chen, Y. Nie, L.B. Yang, W. Wu, J. Liu, CD8 + T cell-Dependent Remodeling of the Tumor Microenvironment Overcomes Chemoresistance. Cancer Immunol. Res. 11, 320–338 (2023)
Article CAS PubMed PubMed Central Google Scholar
X.J. Chen, G.Y. Cheng, L. Zhu, T.Y. Liu, X.Y. Yang, R.C. Liu, Z.J. Ou, S.S. Zhang, W. Tan, D.X. Lin, C. Wu, Alarmin S100A8 imparts chemoresistance of esophageal cancer by reprogramming cancer-associated fibroblasts. Cell. Rep. Med. 5, (2024)
N. Yang, X.X. Li, W.W. Huang, G.L. Ji, W. Luo, F.M. Jiang, H. Zeng, Y.L. Chen, Y. Chen, L.A. Qiao, L. Chen, S. Rafii, W. Wang, A. Zheng, B.S. Ding, Z.W. Cao, MLKL PARylation in the endothelial niche triggers angiocrine necroptosis to evade cancer immunosurveillance and chemotherapy. Nat. Cell Biol. 27, (2025)
X.J. Chu, W.T. Tian, J.Y. Ning, G. Xiao, Y.Q. Zhou, Z.Q. Wang, Z.F. Zhai, G. Tanzhu, J. Yang, R.R. Zhou, Cancer stem cells: advances in knowledge and implications for cancer therapy. Signal Transduct Tar. 9, (2024)
S.C. Su, J.N. Chen, H.R. Yao, J. Liu, S.B. Yu, L.Y. Lao, M.H. Wang, M.L. Luo, Y. Xing, F. Chen, D. Huang, J.H. Zhao, L.B. Yang, D. Liao, F.X. Su, M.F. Li, Q. Liu, E.W. Song, CD10+ GPR77+ Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness, Cell. 172, (2018)
Q.Z. Shi, Q.C. Shen, Y.F. Liu, Y. Shi, W.W. Huang, X. Wang, Z.Q. Li, Y.Y. Chai, H. Wang, X.J. Hu, N. Li, Q. Zhang, X.T. Cao, Increased glucose metabolism in TAMs fuels O-GlcNAcylation of lysosomal Cathepsin B to promote cancer metastasis and chemoresistance. Cancer cell. 40, 1207– (2022)
Article CAS PubMed Google Scholar
H.Y. Li, P.H. Yang, J.H. Wang, J. Zhang, Q.Y. Ma, Y.J. Jiang, Y.N. Wu, T. Han, D.M. Xiang, HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk. J. Hematol. Oncol. 15, (2022)
R. Di Micco, V. Krizhanovsky, D. Baker, F.D. di Fagagna, Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell. Bio. 22, 75–95 (2021)
B.S. Wang, J. Han, J.H. Elisseeff, M. Demaria, The senescence-associated secretory phenotype and its physiological and pathological implications. Nat. Rev. Mol. Cell. Bio. 25, 958–978 (2024)
M. Colucci, M. Sarill, M. Maddalena, A. Valdata, M. Troiani, M. Massarotti, M. Bolis, S. Bressan, A. Kohl, D. Robesti, M. Saponaro, Q. Shi, P. Song, D. Brina, B. Cali, A. Alimonti, Senescence in cancer, Cancer cell. 43, (2025) 1204–1226
Z.N. Dong, Y.H. Luo, Z.C. Yuan, Y. Tian, T.Q. Jin, F. Xu, Cellular senescence and SASP in tumor progression and therapeutic opportunities. Mol. Cancer. 23, (2024)
D. McHugh, I. Durán, J. Gil, Senescence as a therapeutic target in cancer and age-related diseases. Nat. Rev. Drug Discovery. 24, 57–71 (2025)
Article CAS PubMed Google Scholar
L. Zhou, B.Y. Ma, M. Ruscetti, Cellular senescence offers distinct immunological vulnerabilities in cancer. Trends Cancer. 11, 334–350 (2025)
S. Haston, E. Gonzalez-Gualda, S. Morsli, J.F. Ge, V. Reen, A. Calderwood, I. Moutsopoulos, L. Panousopoulos, P. Deletic, G. Carreno, R. Guiho, S. Manshaei, J.M. Gonzalez-Meljem, H.Y. Lim, D.J. Simpson, J. Birch, H.A. Pallikonda, T. Chandra, D. Macias, G.J. Doherty, D.M. Rassl, R.C. Rintoul, M. Signore, I. Mohorianu, A.N. Akbar, J. Gil, D. Muñoz-Espin, J.P. Martinez-Barbera, Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer. Cancer cell. 41, 1242– (2023)
Article CAS PubMed Google Scholar
J.I. Belle, D. Sen, J.M. Baer, X.T. Liu, V.E. Lander, J.Y. Ye, B.E. Sells, B.L. Knolhoff, A. Faiz, L. Kang, G.H. Qian, R.C. Fields, L. Ding, H. Kim, P.P. Provenzano, S.A. Stewart, D.G. Denardo, Senescence Defines a Distinct Subset of Myofibroblasts That Orchestrates Immunosuppression in Pancreatic Cancer, Cancer discovery, 14, 1324–1355 (2024)
L.I. Prieto, I. Sturmlechner, S.I. Graves, C. Zhang, N.P. Goplen, E.S. Yi, J. Sun, H. Li, D.J. Baker, Senescent alveolar macrophages promote early-stage lung tumorigenesis. Cancer cell. 41, 1261– (2023)
Article CAS PubMed PubMed Central Google Scholar
L. Chibaya, K.C. Murphy, K.D. DeMarco, S. Gopalan, H.B. Liu, C.N. Parikh, Y. Lopez-Diaz, M. Faulkner, J.H. Li, J.P. Morris, Y.J. Ho, S.K. Chana, J. Simon, W. Luan, A. Kulick, E. de Stanchina, K. Simin, L.J. Zhu, T.G. Fazzio, S.W. Lowe, M. Ruscetti, EZH2 inhibition remodels the inflammatory senescence-associated secretory phenotype to potentiate pancreatic cancer immune surveillance. Nat. Cancer. 4, 872– (2023)
Article CAS PubMed PubMed Central Google Scholar
G. Zhao, Y.T. Liu, S.Q. Yin, R.X. Cao, Q. Zhao, Y.F. Fu, Y. Du, FOSL1 transcriptionally dictates the Warburg effect and enhances chemoresistance in triple-negative breast cancer. J. Transl Med. 23, (2025)
B. Han, X. Guan, M.Y. Ma, B.L. Liang, L.L. Ren, Y.T. Liu, Y. Du, S.H. Jiang, D. Song, Stiffened tumor microenvironment enhances perineural invasion in breast cancer via integrin signaling. Cell. Oncol. 47, 867–882 (2024)
T.V. Pukhalskaia, T.R. Yurakova, D.A. Bogdanova, O.N. Demidov, Tumor-Associated Senescent Macrophages, Their Markers, and Their Role in Tumor Microenvironment, Biochemistry-Moscow+. 89, 839–852 (2024)
G. Fan, B. Yu, L. Tang, R. Zhu, J. Chen, Y. Zhu, H. Huang, L. Zhou, J. Liu, W. Wang, Z. Tao, F. Zhang, S. Yu, X. Lu, Y. Cao, S. Du, H. Li, J. Li, J. Zhang, H. Ren, O. Gires, H. Liu, X. Wang, J. Qin, H. Wang, TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer. Sci. Transl. Med. 16, eadj5705 (2024)
Article CAS PubMed Google Scholar
B. Tavora, L.E. Reynolds, S. Batista, F. Demircioglu, I. Fernandez, T. Lechertier, D.M. Lees, P.P. Wong, A. Alexopoulou, G. Elia, A. Clear, A. Ledoux, J. Hunter, N. Perkins, J.G. Gribben, Hodivala-Dilke, Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy. Nature. 514, 112– (2014)
Article CAS PubMed PubMed Central Google Scholar
O.C. Olson, H. Kim, D.F. Quail, E.A. Foley, J.A. Joyce, Tumor-Associated Macrophages Suppress the Cytotoxic Activity of Antimitotic Agents. Cell. Rep. 19, 101–113 (2017)
Article CAS PubMed PubMed Central Google Scholar
S.G. Moreno, Depleting Macrophages In Vivo with Clodronate-Liposomes, Methods in molecular biology. (Clifton N J). 1784, 259–262 (2018)
J. Liu, L.Y. Lao, J.N. Chen, J. Li, W.F. Zeng, X.F. Zhu, J.Q. Li, X.M. Chen, L.B. Yang, Y. Xing, F. Chen, D. Huang, X.Q. Zhang, W. Wei, C. Gong, S.Y. Huang, Z.G. Yu, Z.H. Li, L.H. Yang, J.P. Liu, X.Z. Liu, Q.H. Zheng, X.L. Meng, J. Liang, L.Y. Sun, M.S. Zeng, M.F. Li, Q. Liu, S.C. Su, E.R. Song, The IRENA lncRNA converts chemotherapy-polarized tumor-suppressing macrophages to tumor-promoting phenotypes in breast cancer. Nat. Cancer. 2, 457– (2021)
Article CAS PubMed Google Scholar
Y. Zhu, T. Tchkonia, H. Fuhrmann-Stroissnigg, H.M.M. Dai, Y.Y.Y. Ling, M.B. Stout, T. Pirtskhalava, N. Giorgadze, K.O. Johnson, C.B. Giles, J.D. Wren, L.J. Niedernhofer, P.D. Robbins, J.L. Kirkland, Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 15, 428–435 (2016)
Article CAS PubMed PubMed Central Google Scholar
M. Suda, T. Tchkonia, J.L. Kirkland, T. Minamino, Targeting senescent cells for the treatment of age-associated diseases. J. Biochem. 177, 177–187 (2024)
A. Lewinska, P. Przybylski, J. Adamczyk-Grochala, D. Bloniarz, G. Litwinienko, M. Wnuk, Senolysis-Based Elimination of Chemotherapy-Induced Senescent Breast Cancer Cells by Quercetin Derivative with Blocked Hydroxy Groups. Cancers. 14, (2022)
J. Birch, J. Gil, Senescence and the SASP: many therapeutic avenues. Genes Dev. 34, 1565–1576 (2020)
Article CAS PubMed PubMed Central Google Scholar
S. Saha, S. Mukherjee, P. Khan, K. Kajal, M. Mazumdar, A. Manna, S. Mukherjee, S. De, D. Jana, D.K. Sarkar, T. Das, Aspirin Suppresses the Acquisition of Chemoresistance in Breast Cancer by Disrupting an NFκB-IL6 Signaling Axis Responsible for the Generation of Cancer Stem Cells. Cancer Res. 76, 2000–2012 (2016)
Article CAS PubMed Google Scholar
A. Sajid, H. Rahman, S.V. Ambudkar, Advances in the structure, mechanism and targeting of chemoresistance-linked ABC transporters. Nat. Rev. Cancer. 23, 762–779 (2023)
Article CAS PubMed Google Scholar
S. Marimuthu, S. Rauth, K. Ganguly, C.M. Zhang, I. Lakshmanan, S.K. Batra, M.P. Ponnusamy, Mucins reprogram stemness, metabolism and promote chemoresistance during cancer progression. Cancer Metast Rev. 40, 575–588 (2021)
C. Hong, M. Schubert, A.E. Tijhuis, M. Requesens, M. Roorda, A. van den Brink, L.A. Ruiz, P.L. Bakker, T. van der Sluis, W. Pieters, M.T. Chen, R. Wardenaar, B. van der Vegt, D.C.J. Spierings, M. de Bruyn, M.A.T.M. van Vugt, F. Foijer, cGAS-STING drives the IL-6-dependent survival of chromosomally instable cancers. Nature. 607, 366– (2022)
Article CAS PubMed Google Scholar
X.X. Lu, Z.C. Gou, H. Chen, L. Li, F. Chen, C.J. Bao, H. Bu, Z. Zhang, Extracellular matrix cancer-associated fibroblasts promote stromal fibrosis and immune exclusion in triple-negative breast cancer. J. Pathol. 265, 385–399 (2025)
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