scholarly journals Mechanisms of Drug Resistance in Cancer: The Role of Extracellular Vesicles

PROTEOMICS ◽  
2017 ◽  
Vol 17 (23-24) ◽  
pp. 1600375 ◽  
Author(s):  
Priya Samuel ◽  
Muller Fabbri ◽  
David Raul Francisco Carter
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles

scholarly journals Normoxic Tumour Extracellular Vesicles Modulate the Response of Hypoxic Cancer and Stromal Cells to Doxorubicin In Vitro

2020 ◽  
Vol 21 (17) ◽  
pp. 5951
Author(s):  
Laura Patras ◽  
Marcel H. A. M. Fens ◽  
Pieter Vader ◽  
Arjan Barendrecht ◽  
Alina Sesarman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Tumour Microenvironment ◽  
Hypoxia Inducible Factor 1 ◽  
Apoptotic Protein ◽  
Donor Cells

Extracellular vesicles (EV) secreted in the tumour microenvironment (TME) are emerging as major antagonists of anticancer therapies by orchestrating the therapeutic outcome through altering the behaviour of recipient cells. Recent evidence suggested that chemotherapeutic drugs could be responsible for the EV-mediated tumour–stroma crosstalk associated with cancer cell drug resistance. Here, we investigated the capacity of tumour EV (TEV) secreted by normoxic and hypoxic (1% oxygen) C26 cancer cells after doxorubicin (DOX) treatment to alter the response of naïve C26 cells and RAW 264.7 macrophages to DOX. We observed that C26 cells were less responsive to DOX treatment under normoxia compared to hypoxia, and a minimally cytotoxic DOX concentration that mounted distinct effects on cell viability was selected for TEV harvesting. Homotypic and heterotypic pretreatment of naïve hypoxic cancer and macrophage-like cells with normoxic DOX-elicited TEV rendered these cells slightly less responsive to DOX treatment. The observed effects were associated with strong hypoxia-inducible factor 1-alpha (HIF-1α) induction and B-cell lymphoma–extra-large anti-apoptotic protein (Bcl-xL)-mediated anti-apoptotic response in normoxic DOX-treated TEV donor cells, being also tightly connected to the DOX-TEV-mediated HIF-1α induction, as well as Bcl-xL levels increasing in recipient cells. Altogether, our results could open new perspectives for investigating the role of chemotherapy-elicited TEV in the colorectal cancer TME and their modulatory actions on promoting drug resistance.

scholarly journals The Role of Extracellular Vesicles in the Hallmarks of Cancer and Drug Resistance

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1141 ◽  
Author(s):  
Cristina P. R. Xavier ◽  
Hugo R. Caires ◽  
Mélanie A. G. Barbosa ◽  
Rui Bergantim ◽  
José E. Guimarães ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Genetic Material ◽  
Human Tumor ◽  
Current Evidence ◽  
Drug Resistant ◽  
Intercellular Signaling ◽  
Therapeutic Approaches ◽  
Intercellular Exchange

Extracellular vesicles (EVs) mediate intercellular signaling and communication, allowing the intercellular exchange of proteins, lipids, and genetic material. Their recognized role in the maintenance of the physiological balance and homeostasis seems to be severely disturbed throughout the carcinogenesis process. Indeed, the modus operandi of cancer implies the highjack of the EV signaling network to support tumor progression in many (if not all) human tumor malignancies. We have reviewed the current evidence for the role of EVs in affecting cancer hallmark traits by: (i) promoting cell proliferation and escape from apoptosis, (ii) sustaining angiogenesis, (iii) contributing to cancer cell invasion and metastasis, (iv) reprogramming energy metabolism, (v) transferring mutations, and (vi) modulating the tumor microenvironment (TME) by evading immune response and promoting inflammation. Special emphasis was given to the role of EVs in the transfer of drug resistant traits and to the EV cargo responsible for this transfer, both between cancer cells or between the microenvironment and tumor cells. Finally, we reviewed evidence for the increased release of EVs by drug resistant cells. A timely and comprehensive understanding of how tumor EVs facilitate tumor initiation, progression, metastasis and drug resistance is instrumental for the development of innovative EV-based therapeutic approaches for cancer.

scholarly journals Extracellular Vesicles and Cancer Stem Cells in Tumor Progression: New Therapeutic Perspectives

2021 ◽  
Vol 22 (19) ◽  
pp. 10572
Author(s):  
Maria Giovanna Scioli ◽  
Sonia Terriaca ◽  
Elena Fiorelli ◽  
Gabriele Storti ◽  
Giulia Fabbri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Extracellular Vesicles ◽  
Cross Talk ◽  
Cell Populations ◽  
Disease Relapse

Tumor burden is a complex microenvironment where different cell populations coexist and have intense cross-talk. Among them, a heterogeneous population of tumor cells with staminal features are grouped under the definition of cancer stem cells (CSCs). CSCs are also considered responsible for tumor progression, drug resistance, and disease relapse. Furthermore, CSCs secrete a wide variety of extracellular vesicles (EVs) with different cargos, including proteins, lipids, ssDNA, dsDNA, mRNA, siRNA, or miRNA. EVs are internalized by other cells, orienting the microenvironment toward a protumorigenic and prometastatic one. Given their importance in tumor growth and metastasis, EVs could be exploited as a new therapeutic target. The inhibition of biogenesis, release, or uptake of EVs could represent an efficacious strategy to impair the cross-talk between CSCs and other cells present in the tumor microenvironment. Moreover, natural or synthetic EVs could represent suitable carriers for drugs or bioactive molecules to target specific cell populations, including CSCs. This review will discuss the role of CSCs and EVs in tumor growth, progression, and metastasis and how they affect drug resistance and disease relapse. Furthermore, we will analyze the potential role of EVs as a target or vehicle of new therapies.

scholarly journals The Role of Extracellular Vesicles in Mediating Resistance to Anticancer Therapies

2021 ◽  
Vol 22 (8) ◽  
pp. 4166
Author(s):  
Saeideh Maleki ◽  
James Jabalee ◽  
Cathie Garnis
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Targeted Therapies ◽  
Genetic Material ◽  
Cell Communication ◽  
Genetic Alterations ◽  
Damage Repair ◽  
Genetic Mechanisms ◽  
Lipid Bilayer Vesicles

Although advances in targeted therapies have driven great progress in cancer treatment and outcomes, drug resistance remains a major obstacle to improving patient survival. Several mechanisms are involved in developing resistance to both conventional chemotherapy and molecularly targeted therapies, including drug efflux, secondary mutations, compensatory genetic alterations occurring upstream or downstream of a drug target, oncogenic bypass, drug activation and inactivation, and DNA damage repair. Extracellular vesicles (EVs) are membrane-bound lipid bilayer vesicles that are involved in cell–cell communication and regulating biological processes. EVs derived from cancer cells play critical roles in tumor progression, metastasis, and drug resistance by delivering protein and genetic material to cells of the tumor microenvironment. Understanding the biochemical and genetic mechanisms underlying drug resistance will aid in the development of new therapeutic strategies. Herein, we review the role of EVs as mediators of drug resistance in the context of cancer.

scholarly journals The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

2021 ◽  
Vol 22 (8) ◽  
pp. 3964
Author(s):  
Danilo Marimpietri ◽  
Irma Airoldi ◽  
Angelo Corso Faini ◽  
Fabio Malavasi ◽  
Fabio Morandi
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Human Neuroblastoma ◽  
Response To Chemotherapy ◽  
Underlying Mechanisms ◽  
Tumor In Childhood ◽  
Molecular Components

The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. The ability of extracellular vesicles to cross-talk with different cells in the tumor microenvironment and to modulate an anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance will be pinpointed in detail. The results obtained on the role of extracellular vesicles may represent a panel of suggestions potentially useful in practice, due to their involvement in the response to chemotherapy, and, moreover, their ability to predict resistance to standard therapies—all issues of clinical relevance.

scholarly journals Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 132
Author(s):  
Mark Samuels ◽  
Chiara Cilibrasi ◽  
Panagiotis Papanastasopoulos ◽  
Georgios Giamas
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
Cancer Microenvironment ◽  
Bidirectional Communication

Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour microenvironment is now known to be an important contributor to therapy resistance. Several studies have demonstrated that crosstalk with the tumour microenvironment through extracellular vesicles is an important mechanism employed by cancer cells that leads to drug resistance via changes in protein, lipid and nucleic acid cargoes. Moreover, the cargo content enables extracellular vesicles to be used as effective biomarkers for predicting response to treatments and as potential therapeutic targets. This review summarises the literature to date regarding the role of extracellular vesicles in promoting therapy resistance in breast cancer through communication with the tumour microenvironment.

scholarly journals The Role of Extracellular Vesicles as Modulators of the Tumor Microenvironment, Metastasis and Drug Resistance in Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 746 ◽  
Author(s):  
Kodappully S. Siveen ◽  
Afsheen Raza ◽  
Eiman I. Ahmed ◽  
Abdul Q. Khan ◽  
Kirti S. Prabhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Significant Role ◽  
Biological Fluids ◽  
Therapeutic Targets ◽  
Response To Therapy ◽  
High Morbidity

Colorectal cancer (CRC) is one of the most common cancers worldwide, with high morbidity and mortality rates. A number of factors including modulation of the tumor microenvironment, high metastatic capability, and resistance to treatment have been associated with CRC disease progression. Recent studies have documented that tumor-derived extracellular vesicles (EVs) play a significant role in intercellular communication in CRC via transfer of cargo lipids, proteins, DNA and RNAs to the recipient tumor cells. This transfer influences a number of immune-related pathways leading to activation/differentiation/expression of immune cells and modulation of the tumor microenvironment that plays a significant role in CRC progression, metastasis, and drug resistance. Furthermore, tumor-derived EVs are secreted in large amounts in biological fluids of CRC patients and as such the expression analysis of EV cargoes have been associated with prognosis or response to therapy and may be a source of therapeutic targets. This review aims to provide a comprehensive insight into the role of EVs in the modulation of the tumor microenvironment and its effects on CRC progression, metastasis, and drug resistance. On the other hand, the potential role of CRC derived EVs as a source of biomarkers of response and therapeutic targets will be discussed in detail to understand the dynamic role of EVs in CRC diagnosis, treatment, and management.

scholarly journals Translational Potential of RNA Derived From Extracellular Vesicles in Multiple Myeloma

2021 ◽  
Vol 11 ◽  
Author(s):  
Antonia Reale ◽  
Tiffany Khong ◽  
Sridurga Mithraprabhu ◽  
Andrew Spencer
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Minimally Invasive ◽  
Extracellular Vesicles ◽  
Cross Talk ◽  
Stromal Cells ◽  
Biological Features ◽  
Isolation And Characterization

The cross-talk between tumour cells and stromal cells is a hallmark of multiple myeloma (MM), a blood cancer that still remains incurable despite increased knowledge of its biology and advances in its treatment. Extracellular vesicles (EVs) derived from both tumour and stromal cells have been shown to play an important role in mediating this cross-talk ultimately favouring MM progression and drug resistance. Furthermore, EVs and their content including RNA (EV-RNA) have been successfully isolated from blood and are being explored as liquid biomarkers in MM with the potential to improve diagnosis and monitoring modalities with a minimally-invasive and repeatable analysis, i.e. liquid biopsy. In this review, we describe both the role of EV-RNA in defining the biological features of MM and their potential translational relevance as liquid biomarkers, therapeutic targets and delivery systems. We also discuss the limitations and technical challenges related to the isolation and characterization of EVs and provide a perspective on the future of MM-derived EV-RNA in translational research.

Methods to unravel the role of HDAC10 in autophagy-related drug resistance

2015 ◽  
Vol 227 (06/07) ◽  
Author(s):  
J Fabian ◽  
J Ridinger ◽  
O Witt ◽  
I Oehme
Keyword(s):  
Drug Resistance ◽  
Related Drug
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