The role of cancer-associated fibroblast-derived exosomes in chemotherapy resistance in lung cancer

Xiaoyu Cui¹Nan Tang¹Huan Xiong^2*

• ¹南昌大学, 江西省南昌市, China
• ²Jiujiang University Medical College, Jiujiang, China

Globally, lung cancer ranks as the second most prevalent type of cancer and stands as the primary cause of cancer-related fatalities. Despite advances in lung cancer therapies, chemotherapy resistance remains a major challenge, and increasing evidence points to the role of the tumor microenvironment (TME) as key mediators. Among the key components of the TME are cancer-associated fibroblasts (CAFs), recent studies have demonstrated that cancer-associated fibroblast-derived exosomes that play a key role in modulating chemotherapy response. However, there are still many deficiencies in research on exploring the significance of exosomes derived from CAFs in promoting chemotherapy resistance in lung cancer cells. This review systematically examines the TME's role in disease progression, emphasizing gaps in understanding exosome-mediated resistance mechanisms originating from cancer-associated fibroblasts. The analysis delineates CAFs' dual role as both tumor promoters and therapeutic obstacles, followed by exosomes' emerging function as intercellular communication vehicles in resistance development. Key discussion points include: CAF origin and microenvironmental interactions, exosome biogenesis ,mechanisms of chemotherapy resistance in lung cancer ,and clinical significance and limitations of mechanism study. The review synthesizes findings to propose a conceptual framework for targeting CAF-derived exosomes(CAF-Exos), highlighting their potential as both resistance mediators and therapeutic targets.