Journal
DRUG RESISTANCE UPDATES
Volume 62, Issue -, Pages -Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.drup.2022.100833
Keywords
Cancer drug resistance; Extracellular vesicles; Tumor microenvironment; Intercellular transfer of drug resistance; competences
Categories
Funding
- COST (European Cooperation in Science and Technology) [17104]
- FEDER -Fundo Europeu de Desenvolvimento Regional through COMPETE
- FCT -Foundation for Science and Technology [POCI-01-0145-FEDER-030457, NORTE-01-0145-FEDER-000051]
- Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)
- Cancer Center Amsterdam
- KWF [13598]
- AIRC
- Fondazione Cassa di Risparmio di Torino [IG-24444]
- FCT -Fundac ~ao para a Ci <^>encia e Tecnologia [2020.1648]
- [SFRH/BPD/122871/2016]
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/122871/2016] Funding Source: FCT
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This review summarizes the role of extracellular vesicles (EVs) in the transfer of drug resistance traits to cancer cells and the importance of interaction between tumor microenvironment cells and tumor cells. It also discusses the potential clinical applications of EVs as biomarkers of drug resistance.
Drug resistance remains a major hurdle to successful cancer treatment, being accountable for approximately 90% of cancer-related deaths. In the past years, increasing attention has been given to the role of extracellular vesicles (EVs) in the horizontal transfer of drug resistance in cancer. Indeed, many studies have described the dissemination of therapy resistance traits mediated by EVs, which may be transferred from drug resistant tumor cells to their drug sensitive counterparts. Importantly, different key players of drug resistance have been identified in the cargo of those EVs, such as drug efflux pumps, oncoproteins, antiapoptotic proteins, or microRNAs, among others. Interestingly, the EVs-mediated crosstalk between cells from the tumor microenvironment (TME) and tumor cells has emerged as another important mechanism that leads to cancer cells drug resistance. Recently, the cargo of the TME-derived EVs responsible for the transfer of drug resistance traits has also become a focus of attention. In addition, the possible mechanisms involved in drug sequestration by EVs, likely to contribute to cancer drug resistance, are also described and discussed herein. Despite the latest scientific advances in the field of EVs, this is still a challenging area of research, particularly in the clinical setting. Therefore, further investigation is needed to assess the relevance of EVs to the failure of cancer patients to drug treatment, to identify biomarkers of drug resistance in the EV???s cargo, and to develop effective therapeutic strategies to surmount drug resistance. This up-to-date review summarizes relevant literature on the role of EVs in the transfer of drug resistance competences to cancer cells, and the relevance of tumor cells and of TME cells in this process. Finally, this knowledge is integrated with a discussion of possible future clinical applications of EVs as biomarkers of drug resistance.
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