Harnessing cancer stem cell-derived exosomes to improve cancer therapy

Cancer stem cells (CSCs) are the key "seeds" for tumor initiation and development, metastasis, and recurrence. Because of the function of CSCs in tumor development and progression, research in this field has intensified and CSCs are viewed as a new therapeutic target. Exosomes carrying a wide range of DNA, RNA, lipids, metabolites, and cytosolic and cell-surface proteins are released outside of the originating cells through the fusion of multivesicular endosomes or multivesicular bodies with the plasma membrane. It has become evident that CSC-derived exosomes play a significant role in almost all "hallmarks" of cancer. For example, exosomes from CSCs can maintain a steady state of self-renewal in the tumor microenvironment and regulate microenvironmental cells or distant cells to help cancer cells escape immune surveillance and induce immune tolerance. However, the function and therapeutic value of CSC-derived exosomes and the underlying molecular mechanisms are still largely undefined. To provide an overview of the possible role of CSC-derived exosomes and targeting strategies, we summarize relevant research progress, highlight the potential impact of detecting or targeting CSC-derived exosomes on cancer treatment, and discuss opportunities and challenges based on our experience and insights in this research area. A more thorough understanding of the characteristics and function of CSC-derived exosomes may open new avenues to the development of new clinical diagnostic/prognostic tools and therapies to prevent tumor resistance and relapse.