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Review
. 2025 Sep 27.
doi: 10.1007/s00210-025-04635-5. Online ahead of print.

CAF-derived exosomes: orchestrators of dysregulated signaling pathways in breast cancer progression

Almuthana K Hameed  1 , Safia Obaidur Rab  2 , Thanaa Amir Ahmed  3 , Muktesh Chandra  4 , Jaafaru Sani Mohammed  5 , Renukajyothi S  6 , Priya Priyadarshini Nayak  7 , Prakhar Tomar  8 , Ahmed Hussn  9   10   11 , Abbas Fadhel Ali  12
Affiliations
Review

CAF-derived exosomes: orchestrators of dysregulated signaling pathways in breast cancer progression

Almuthana K Hameed et al. Naunyn Schmiedebergs Arch Pharmacol. .

Abstract

Cancer-associated fibroblasts (CAFs) play a pivotal role in breast cancer (BC) progression by modulating the tumor microenvironment through exosome-mediated interactions. CAF-derived exosomes are rich in bioactive molecules such as metabolites, proteins, and non-coding RNAs that influence metabolic reprogramming in BC cells. These exosomes facilitate the transfer of metabolic enzymes and signaling molecules that enhance glycolysis, lipid metabolism, and oxidative phosphorylation, thereby supporting tumor growth, therapy resistance, and metastasis. This review highlights the molecular mechanisms underlying the role of CAF-derived exosomes in BC metabolism, with a focus on their contributions to metabolic plasticity and tumor progression. Potential therapeutic strategies targeting CAF exosome biogenesis, release, or uptake will also be discussed to shed light on innovative approaches for disrupting this metabolic symbiosis.

Keywords: Breast cancer; Cancer-associated fibroblasts; Exosomes; Tumor microenvironment.

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Conflict of interest statement

Declarations. Ethical approval: Not applicable. Competing interests: The authors declare no competing interests. AI and third-party statement: The authors declare that all data were generated in-house, that no paper mill was used and that no AI tool has been used for the generation of text or figures.

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