Abstract
This review summarizes recent findings on the role of M2 tumor-associated macrophages (TAMs) and their exosome-derived non-coding RNAs (ncRNAs) in cancer cell resistance to therapeutics. M2 TAMs promote angiogenesis, suppress immune responses, and facilitate metastasis, thereby creating a tumor-supporting microenvironment. A range of antitumor drugs, including 5-FU, cisplatin, and gemcitabine, are mediated by M2 exosomes, each with distinct mechanisms of action. M2 exosomes transfer drug resistance capabilities via extracellular vesicles, especially exosomes containing miRNAs, lncRNAs, and circRNAs. These exosome mediate the development of tumor drug resistance by regulating signaling pathways such as PI3K/AKT, MAPK/ERK, Wnt/β-catenin M2 exosomes can regulate cellular responses by delivering bioactive molecules, including proteins, lipids, and ncRNA, which can also modulate cellular reactions to ionizing radiation, ultraviolet light, and chemotherapeutic agents. Targeting M2 TAMs and their exosome-mediated ncRNAs may offer new strategies to overcome drug resistance in cancer.