Extracellular vesicles: Unveiling the hidden force behind cancer drug resistance

Despite significant advancements in cancer treatment, drug resistance remains a persistent challenge. Cancer cells can often develop resistance to treatments such as chemotherapy, radiotherapy, and immunotherapy, leading to reduced treatment efficacy. Recent research published in Medcomm-Oncology reveals that extracellular vesicles (EVs) play a central role in facilitating this resistance by acting as "messengers" between cells.

The research team, led by Prof. Jun Yang from Kunming Medical University, reviewed how EVs, which are tiny lipid-bound particles released by cells, transfer proteins, RNA, DNA, and other molecules between cancer cells and their microenvironment. These EVs carry resistance-related factors, helping sensitive cancer cells acquire drug resistance from already resistant ones. This intercellular communication not only affects the cancer cells themselves but also involves cells in the tumor microenvironment, such as fibroblasts and immune cells, enhancing tumor growth and therapy resistance.

One key example is in chemotherapy resistance, where cancer cells release EVs loaded with long noncoding RNAs like AC116025.2. These RNAs interact with sensitive cancer cells, allowing them to develop resistance to the widely used chemotherapy drug, 5-FU. Similarly, in radiotherapy, EVs have been shown to carry miRNAs that inhibit apoptosis (programmed cell death) in cancer cells, making them resistant to radiation.

Beyond therapy resistance, EVs are emerging as promising biomarkers due to their stability and ease of detection in bodily fluids. By monitoring the molecular cargo inside EVs, clinicians may be able to predict which tumors are likely to develop resistance to treatment. Moreover, targeting EVs themselves—by preventing their production or blocking their uptake by cancer cells—has the potential to restore treatment sensitivity in resistant tumors.

According to Prof. Yang, "Understanding the mechanisms of EV-mediated drug resistance opens up new avenues for treatment. By targeting EVs, we can potentially reverse resistance and improve the efficacy of current therapies."

This research highlights the urgent need for innovative approaches in cancer treatment, focusing on the manipulation of EVs to curb therapy resistance and improve patient outcomes. The review offers a comprehensive understanding of EV-mediated communication in cancer, paving the way for future studies to explore their potential as both therapeutic targets and diagnostic tools.

See the article: 

Extracellular vesicles in cancer drug resistance: mechanistic insights and therapeutic implications

https://doi.org/10.1002/mog2.94