The Role of Extracellular Vesicles in the Development of a Cancer Stem Cell Microenvironment Niche and Potential Therapeutic Targets: A Systematic Review

Simple Summary Cancer stem cells (CSCs) are cancer cells that possess traits usually attributed to stem cells. An increase in CSCs can lead to more rapid cancer progression, treatment resistance and the increased likelihood of recurrence. To promote CSC survival and associated cancer progression, cancer cells enter into reciprocal crosstalk with the surrounding tissue environment, as well as with distant metastatic sites. This mechanism of communication relies, in part, on secreted factors, of which extracellular vesicles (EVs) are thought to have a critical role. This systematic review evaluates the current knowledge of cancer communication via EVs to alter the microenvironment to increase the survival and maintenance of CSCs. A total of 16 studies spanning the EV content, pathway alterations and CSC-targeting treatments provide new insights into how EVs mediate CSC traits and identify the gaps in our understanding of how modulation of the microenvironment plays a key role. Cancer stem cells (CSCs) have increasingly been shown to be a crucial element of heterogenous tumors. Although a relatively small component of the population, they increase the resistance to treatment and the likelihood of recurrence. In recent years, it has been shown, across multiple cancer types (e.g., colorectal, breast and prostate), that reciprocal communication between cancer and the microenvironment exists, which is, in part, facilitated by extracellular vesicles (EVs). However, the mechanisms of this method of communication and its influence on CSC populations is less well-understood. Therefore, the aim of this systematic review is to determine the evidence that supports the role of EVs in the manipulation of the tumor microenvironment to promote the survival of CSCs. Embase and PubMed were used to identify all studies on the topic, which were screened using PRISMA guidelines, resulting in the inclusion of 16 studies. These 16 studies reported on the EV content, pathways altered by EVs and therapeutic targeting of CSC through EV-mediated changes to the microenvironment. In conclusion, these studies demonstrated the role of EV-facilitated communication in maintaining CSCs via manipulation of the tumor microenvironment, demonstrating the potential of creating therapeutics to target CSCs. However, further works are needed to fully understand the targetable mechanisms upon which future therapeutics can be based.

Automated summary

Cancer stem cells (CSCs) possess traits of stem cells and an increase in CSCs can lead to faster cancer progression, treatment resistance, and higher recurrence rates. Communication via extracellular vesicles (EVs) plays a crucial role in altering the microenvironment to promote the survival and maintenance of CSCs. Further research is needed to fully understand the mechanisms that can be targeted for developing therapeutics to specifically target CSCs.