Fig. 3

Mechanisms of exosome-induced drug resistance in lung cancer: A Exosomes, derived from CAFs and drug-resistant tumor cells, can be efficiently internalized by drug-sensitive cells. Subsequently, the contents of these exosomes, including nucleic acids, miRNA, lncRNA, circRNA and proteins, play a significant role in transmitting the drug-resistance phenotype to the drug-sensitive cells. Cancer cells secrete exosomes that transfer miRNAs to fibroblasts in the TME, leading to the differentiation of CAFs and conferring drug resistance in cancer cells by stimulating metastasis and proliferation while suppressing the pro-apoptotic function of FOXO3a and activating the mTOR/PTEN/P13K/ATK signaling pathway. This activation is directly linked to the inhibition of apoptosis and tumor progression, effectively preventing drug-induced apoptosis. Furthermore, exosomes can enhance drug resistance in sensitive cells by transferring ABC transporters, which are responsible for actively expelling drugs out of the cell. B Therapeutic exosomes can be loaded with therapeutic drugs and miRNAs in vitro. Exosomes loaded with drugs can be taken up by tumor cells, directly causing their death by altering the transcriptome and TME, affecting growth, proliferation, angiogenesis, promoting EMT, and even impacting drug resistance. Moreover, the surface markers of these exosomes can be modified in vitro to enhance their ability to target tumors. Exosomes can also serve as stimulators for DC vaccines, promoting immune responses. Exosomes expressing tumor-associated antigens can stimulate DCs, enabling them to activate T cells, ultimately leading to the destruction of tumor cells. Figure created with BioRender.com