TY - JOUR
T1 - Role of exosomes in transferring chemoresistance through modulation of cancer glycolytic cell metabolism
AU - Vahabi, Mahrou
AU - Comandatore, Annalisa
AU - Franczak, Marika A.
AU - Smolenski, Ryszard T.
AU - Peters, Godefridus J.
AU - Morelli, Luca
AU - Giovannetti, Elisa
N1 - Funding Information: Elisa Giovannetti , MD, PhD. received her M.D. and Ph.D. with full marks and from the University of Pisa, Italy, in 2000 and 2007, respectively. Between 2001 and 2004, she contributed to translational studies on pharmacogenetics as clinical fellow in Pharmacology in the Department of Oncology of Pisa University. Since 2006 she collaborated with the Department of Medical Oncology at VU University Medical Center (VUmc), Amsterdam, The Netherlands, to set-up a line of research on (epi)genetic determinants of drug activity and molecular mechanisms underlying chemoresistance in pancreatic and lung cancer. She was promoted to Associate Professor in 2016, received the habilitation as Full Professor in 2022, and she is also working as PI of a Start-Up lab at the Fondazione Pisana per la Scienza, Pisa, Italy. Her current research interests include also the role of liquid biopsies in early diagnosis and prediction of drug activity. She is actively involved, as elected chair, in research projects within the “Pharmacology and Molecular Mechanism Group” group of the EORTC (EORTC-PAMM), as well as in the European Pancreatic Club (EPC). She successfully requested funding from the Netherlands Organization for Scientific Research (NWO, VENI grant), “Marie Curie” and COST European Initiatives (H2020-MSCA-RISE “Alise” and COST “Stratagem”), Italian Association for Research against Cancer (AIRC, Start-Up and IG grants), Cancer Center Amsterdam (CCA) Foundation, and Dutch Cancer Society (KWF). Dr. Giovannetti is author or co-author of > 350 scientific publications in peer reviewed journals, with an H-index of 64 (Google Scholar), she has been invited for > 130 Selected/Invited Lectures in international meetings, seminars and webinars and she is Deputy Editor of Critical Reviews in Oncology and Hematology, Associate Editor of Cancer Chemotherapy and Pharmacology, Cellular Oncology, Cancers, and Journal of Chemotherapy. Funding Information: This research was funded by CCA Foundation (2018) (EG), KWF ( 11957 ) (EG) and AIRC ( IG-24444 ) (EG), PANOMICS – Fondazione Pisa grant (LM, EG), and National Science Centre of Poland ( 2018/31/B/NZ7/02909 ) (MF, EG, GJP, RTS). Publisher Copyright: © 2023 The Authors
PY - 2023/10
Y1 - 2023/10
N2 - Chemoresistance constitute a major obstacle in cancer treatment, leading to limited options and decreased patient survival. Recent studies have revealed a novel mechanism of chemoresistance acquisition: the transfer of information via exosomes, small vesicles secreted by various cells. Exosomes play a crucial role in intercellular communication by carrying proteins, nucleic acids, and metabolites, influencing cancer cell behavior and response to treatment. One crucial mechanism of resistance is cancer metabolic reprogramming, which involves alterations in the cellular metabolic pathways to support the survival and proliferation of drug-resistant cancer cells. This metabolic reprogramming often includes increased glycolysis, providing cancer cells with the necessary energy and building blocks to evade the effects of chemotherapy. Notably, exosomes have been found to transport glycolytic enzymes, as identified in proteomic profiling, leading to the reprogramming of metabolic pathways, facilitating altered glucose metabolism and increased lactate production. As a result, they profoundly impact the tumor microenvironment, promoting tumor progression, survival, immune evasion, and drug resistance.Understanding the complexities of such exosome-mediated cell-to-cell communication might open new therapeutic avenues and facilitate biomarker development in managing cancers characterized by aggressive glycolytic features. Moreover, given the intricate nature of metabolic abnormalities combining future exosome-based-targeted therapies with existing treatments like chemotherapy, immunotherapy, and targeted therapies holds promise for achieving synergistic effects to overcome resistance and improve cancer treatment outcomes.
AB - Chemoresistance constitute a major obstacle in cancer treatment, leading to limited options and decreased patient survival. Recent studies have revealed a novel mechanism of chemoresistance acquisition: the transfer of information via exosomes, small vesicles secreted by various cells. Exosomes play a crucial role in intercellular communication by carrying proteins, nucleic acids, and metabolites, influencing cancer cell behavior and response to treatment. One crucial mechanism of resistance is cancer metabolic reprogramming, which involves alterations in the cellular metabolic pathways to support the survival and proliferation of drug-resistant cancer cells. This metabolic reprogramming often includes increased glycolysis, providing cancer cells with the necessary energy and building blocks to evade the effects of chemotherapy. Notably, exosomes have been found to transport glycolytic enzymes, as identified in proteomic profiling, leading to the reprogramming of metabolic pathways, facilitating altered glucose metabolism and increased lactate production. As a result, they profoundly impact the tumor microenvironment, promoting tumor progression, survival, immune evasion, and drug resistance.Understanding the complexities of such exosome-mediated cell-to-cell communication might open new therapeutic avenues and facilitate biomarker development in managing cancers characterized by aggressive glycolytic features. Moreover, given the intricate nature of metabolic abnormalities combining future exosome-based-targeted therapies with existing treatments like chemotherapy, immunotherapy, and targeted therapies holds promise for achieving synergistic effects to overcome resistance and improve cancer treatment outcomes.
KW - Cancer metabolism
KW - Cell-to-cell communication
KW - Chemoresistance
KW - Exosomes
KW - Glycolysis
UR - http://www.scopus.com/inward/record.url?scp=85166643419&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cytogfr.2023.07.004
DO - https://doi.org/10.1016/j.cytogfr.2023.07.004
M3 - Review article
C2 - 37541790
SN - 1359-6101
VL - 73
SP - 163
EP - 172
JO - Cytokine & Growth Factor Reviews
JF - Cytokine & Growth Factor Reviews
ER -