Macrophage-derived exosomes in cancer: a double-edged sword with therapeutic potential

Liu, Long; Zhang, Siying; Ren, Yuqing; Wang, Ruizhi; Zhang, Yuyuan; Weng, Siyuan; Zhou, Zhaokai; Luo, Peng; Cheng, Quan; Xu, Hui; Ba, Yuhao; Zuo, Anning; Liu, Shutong; Liu, Zaoqu; Han, Xinwei

doi:10.1186/s12951-025-03321-1

Journal of Nanobiotechnology

Table 3 Tumor-associated macrophage-derived exosomes in cancer therapy resistance

From: Macrophage-derived exosomes in cancer: a double-edged sword with therapeutic potential

Clinical therapy	Cancer type	Drug	Key cargo	Expression	Mechanisms	References
Chemotherapy	GC	Cisplatin	miR-21	Up-regulated	Activate PI3K/AKT signaling pathway by down-regulating PTEN to promote cisplatin resistance	[105]
	GC	Cisplatin	miR-588	Up-regulated	Target and down-regulate CYLD to promote cisplatin resistance	[178]
	GC	Cisplatin	IncRNA CRNDE	Up-regulated	Activate PI3K/AKT signaling pathway by facilitating NEDD4-1-mediated PTEN ubiquitination to promote cisplatin resistance	[179]
	GC	Doxorubicin	miR-223	Up-regulated	Target FBXW7 to impair doxorubicin sensitivity, which may be induced by EMT mechanically	[104]
	GC	Oxaliplatin	circ 0008253	Up-regulated	Probably promote oxaliplatin resistance by up-regulating ABCG2 levels	[180]
	EOC	Cisplatin	miR-223	Up-regulated	Activate PI3K/AKT signaling pathway by down-regulating PTEN to promote cisplatin resistance under hypoxia	[103]
	EOC	Cisplatin	miR-221-3p	Up-regulated	Activate AKT signaling pathway by down-regulating ADAMTS6 to promote EOC cell proliferation, adhesion, migration, and multidrug resistance	[181]
	PDAC	Gemcitabine	miR-365	Up-regulated	Up-regulate the triphospho-nucleotide pool and induce the enzyme cytidine deaminase to inactivate gemcitabine	[182]
	GBM	Temozolomide	miR-21	Up-regulated	Activate STAT3/AKT signaling pathway by targeting and down-regulating PDCD4 to promote temozolomide resistance	[106]
	LC	Cisplatin	miR-3679-5p	Up-regulated	Suppress NEDD4L-mediated c-Myc ubiquitination to increase aerobic glycolysis and promote cisplatin resistance	[183]
Radiotherapy	EC	N/A	Has_circ_0001610	Up-regulated	Cyclin B1 levels that are up-regulated by miR-139-5p prevent EC cells from arresting at the G2/M checkpoint thus decreasing the radiosensitivity	[184]
	LC	N/A	lncRNA AGAP2-AS1	Up-regulated	Weaken the radiosensitivity through down-regulating miR-296 and upregulating NOTCH2	[185]
Targeted therapy	NSCLC	Osimertinib	lncRNA MSTRG.292666.16	Up-regulated	Down-regulate miR-6836-5p and activate MAPK pathway to promote osimertinib resistance	[186]
	NSCLC	Gefitinib	N/A	N/A	Promote gefitinib resistance through the aberrant activation of the AKT, ERK1/2, and STAT3 pathways	[187]
Immunotherapy	GC/CRC	Anti-PD-1 antibody	ApoE	Up-regulated	Down-regulating MHC-I expression on the cancer cells surface by suppressing BiP	[188]
	TC	Anti-PD-1 antibody	miR-21-5p	Up-regulated	Down-regulate METTL3 and trigger the demethylation and stabilization of CD70 mRNA, which promotes Tregs infiltration and induces CD8⁺ T cells exhaustion	[189]
Ferroptosis-based therapy	CC	Erastin	miRNA-660-5p	Up-regulated	Target and inhibit the expression of ALOX15 to suppress erastin-induced ferroptosis	[190]

GC gastric cancer, EOC epithelial ovarian cancer, PDAC Pancreatic ductal adenocarcinoma, GBM glioblastoma, LC lung cancer, EC endometrial cancer, NSCLC non-small cell lung cancer, CRC colorectal cancer, TC thyroid cancer, CC cervical cancer, PI3K Phosphatidylinositol-3-kinas, PTEN phosphatase and tensin homolog, FBXW7 F-box and WD repeat domain-containing 7, EMT epithelial-to-mesenchymal transition, CYLD cylindromatosis, NEDD4 neuronally expressed developmentally downregulated 4, ABCG2 ATP binding cassette subfamily G member 2, ADAMTS6 a disintegrin and metalloproteinase with thrombospondin motifs 6, STAT3 signal transducer and activator of transcription 3, PDCD4 programmed cell death protein 4, c-Myc cellular-myelocytomatosis viral oncogene, NOTCH2 notch homologous protein 2, MAPK mitogen-activated protein kinase, ERK extracellular regulated protein kinases, ALOX15 arachidonic acid 15-lipoxygenase

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ISSN: 1477-3155

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