TY - JOUR
T1 - The role of extracellular vesicles in the transfer of drug resistance competences to cancer cells
AU - Xavier, Cristina P. R.
AU - Belisario, Dimas Carolina
AU - Rebelo, Rita
AU - Assaraf, Yehuda G.
AU - Giovannetti, Elisa
AU - Kopecka, Joanna
AU - Vasconcelos, M. Helena
N1 - Funding Information: This article is based upon work from COST Action 17104 STRATAGEM, supported by COST (European Cooperation in Science and Technology). The Vasconcelos group is supported by FEDER – Fundo Europeu de Desenvolvimento Regional through COMPETE 2020 and by FCT - Foundation for Science and Technology, in the framework of project POCI-01-0145-FEDER-030457 and also by project “Cancer Research on Therapy Resistance: From Basic Mechanisms to Novel Targets” - NORTE-01-0145-FEDER-000051, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement , through the European Regional Development Fund (ERDF). The Giovannetti group is supported by Cancer Center Amsterdam 2018 and KWF#13598 grants (The Netherlands), and AIRC IG-24444 grant (Italy). The Kopecka group is supported by Fondazione Cassa di Risparmio di Torino ID 2020.1648. Cristina P.R. Xavier is supported by FCT - Fundação para a Ciência e Tecnologia and FSE - Fundo Social Europeu , Portugal, through the post-doc grant SFRH/BPD/122871/2016 . Funding Information: This article is based upon work from COST Action 17104 STRATAGEM, supported by COST (European Cooperation in Science and Technology). The Vasconcelos group is supported by FEDER ? Fundo Europeu de Desenvolvimento Regional through COMPETE 2020 and by FCT - Foundation for Science and Technology, in the framework of project POCI-01-0145-FEDER-030457 and also by project ?Cancer Research on Therapy Resistance: From Basic Mechanisms to Novel Targets? - NORTE-01-0145-FEDER-000051, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The Giovannetti group is supported by Cancer Center Amsterdam 2018 and KWF#13598 grants (The Netherlands), and AIRC IG-24444 grant (Italy). The Kopecka group is supported by Fondazione Cassa di Risparmio di Torino ID 2020.1648. Cristina P.R. Xavier is supported by FCT - Funda??o para a Ci?ncia e Tecnologia and FSE - Fundo Social Europeu, Portugal, through the post-doc grant SFRH/BPD/122871/2016. Publisher Copyright: © 2022
PY - 2022/5/1
Y1 - 2022/5/1
N2 - 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.
AB - 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.
KW - Cancer drug resistance
KW - Extracellular vesicles
KW - Intercellular transfer of drug resistance competences
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85128197831&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.drup.2022.100833
DO - https://doi.org/10.1016/j.drup.2022.100833
M3 - Review article
C2 - 35429792
SN - 1368-7646
VL - 62
JO - Drug resistance updates
JF - Drug resistance updates
M1 - 100833
ER -