scholarly journals Boron-containing delocalised lipophilic cations for the selective targeting of cancer cells

MedChemComm ◽  
2017 ◽  
Vol 8 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Calabrese Gianpiero ◽  
Daou Anis ◽  
Rova Aikaterini ◽  
Tseligka Eirini ◽  
Vizirianakis S. Ioannis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Treatments ◽  
Lipophilic Cations ◽  
Selective Targeting

To limit the incidence of relapse, cancer treatments must not promote the emergence of drug resistance in tumour and cancer stem cells.

scholarly journals Role of Exosomal miRNAs and the Tumor Microenvironment in Drug Resistance

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1450 ◽  
Author(s):  
Patrick Santos ◽  
Fausto Almeida
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapy Resistance ◽  
Chemotherapeutic Agents ◽  
Exosomal Mirnas ◽  
Key Factor

Tumor microenvironment (TME) is composed of different cellular populations, such as stromal, immune, endothelial, and cancer stem cells. TME represents a key factor for tumor heterogeneity maintenance, tumor progression, and drug resistance. The transport of molecules via extracellular vesicles emerged as a key messenger in intercellular communication in the TME. Exosomes are small double-layered lipid extracellular vesicles that can carry a variety of molecules, including proteins, lipids, and nucleic acids. Exosomal miRNA released by cancer cells can mediate phenotypical changes in the cells of TME to promote tumor growth and therapy resistance, for example, fibroblast- and macrophages-induced differentiation. Cancer stem cells can transfer and enhance drug resistance in neighboring sensitive cancer cells by releasing exosomal miRNAs that target antiapoptotic and immune-suppressive pathways. Exosomes induce drug resistance by carrying ABC transporters, which export chemotherapeutic agents out of the recipient cells, thereby reducing the drug concentration to suboptimal levels. Exosome biogenesis inhibitors represent a promising adjunct therapeutic approach in cancer therapy to avoid the acquisition of a resistant phenotype. In conclusion, exosomal miRNAs play a crucial role in the TME to confer drug resistance and survivability to tumor cells, and we also highlight the need for further investigations in this promising field.

scholarly journals Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210

2019 ◽  
Vol 43 (1) ◽  
pp. 123-136 ◽  
Author(s):  
Zhiyong Yang ◽  
Ning Zhao ◽  
Jing Cui ◽  
Heshui Wu ◽  
Jiongxin Xiong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Expression Levels ◽  
Pancreatic Cancer Cells ◽  
Pancreatic Cancer Stem Cells

Abstract Purpose Gemcitabine (GEM)-based chemotherapy is the first-line treatment for locally advanced pancreatic cancer. GEM resistance, however, remains a significant clinical challenge. Here, we investigated whether exosomes derived from GEM-resistant pancreatic cancer stem cells (CSCs) mediate cell-cell communication between cells that are sensitive or resistant to GEM and, by doing so, regulate drug resistance. Methods GEM-sensitive BxPC-3-derived BxS and PANC-1 pancreatic cancer cells were cultured with exosomes extracted from CSCs isolated from GEM-resistant BxPC-3-derived BxR cells (BxR-CSC). The effect of exosomes on drug resistance, cell cycle progression, apoptosis and miRNA expression was evaluated in BxS and PANC-1 cells. Relevant miRNAs associated with GEM resistance were identified and the role of miR-210 in conferring drug resistance was examined in vitro and in vivo. Results BxR-CSC-derived exosomes induced GEM resistance, inhibited GEM-induced cell cycle arrest, antagonized GEM-induced apoptosis, and promoted tube formation and cell migration in BxS and PANC-1 cells. Elevated miR-210 expression levels were detected in BxR-CSCs and BxR-CSC-derived exosomes compared to those in BxS-CSCs and BxS-CSC-derived exosomes. In addition, increased expression levels of miR-210 were observed in BxS and PANC-1 cells cultured with BxR-CSC-derived exosomes upon exposure to GEM in a dose-dependent manner. Also, a series of biological changes was observed in BxS cells after transfection with miR-210 mimics, including activation of the mammalian target of rapamycin (mTOR) signaling pathway, and these changes were similar to those triggered by BxR-CSC-derived exosomes. Conclusions Our findings suggest that exosomes derived from GEM-resistant pancreatic cancer stem cells mediate the horizontal transfer of drug-resistant traits to GEM-sensitive pancreatic cancer cells by delivering miR-210.

scholarly journals Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1896 ◽  
Author(s):  
Kevin Dzobo ◽  
Dimakatso Alice Senthebane ◽  
Chelene Ganz ◽  
Nicholas Ekow Thomford ◽  
Ambroise Wonkam ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Treatment Strategies ◽  
Cancer Recurrence ◽  
Therapy Resistance ◽  
Microenvironmental Factors ◽  
Novel Treatment Strategies

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance culminating in relapse continues to be associated with fatal disease. The cancer stem cell theory posits that tumors are driven by specialized cancer cells called cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterized in many cancers with data illustrating that CSCs display great abilities to self-renew, resist therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ATP-binding cassette (ABC) membrane transporters, activation of several survival signaling pathways and increased immune evasion as well as DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we revisit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.

scholarly journals Leukemic stem cells: from metabolic pathways and signaling to a new concept of drug resistance targeting.

2007 ◽  
Vol 54 (4) ◽  
pp. 717-726 ◽  
Author(s):  
Jan Styczynski ◽  
Tomasz Drewa
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Small Subset ◽  
Stem Cell Markers ◽  
Beta Catenin ◽  
Nf Kappab ◽  
Long Term Behavior

Cancer stem cells are a small subset of cancer cells constituting a reservoir of self-sustaining cells with the exclusive ability to self-renew and maintain the tumor. These cells are identified by specific stem cell markers: antigens, molecules and signaling pathways. Transcription factors and molecules associated with oncogenesis, such as NF-kappaB, Bmi-1, Notch, WNT beta-catenin, Sonic hedgehog and their biochemical pathways, active only in a small minority of cancer cells might play key roles in determining the biology and the overall long-term behavior of a tumor. The molecules and pathways specific for cancer stem cells, which contribute to their drug resistance, are potential targets for new therapeutic strategies.

scholarly journals MiRNA-mediated EMT and CSCs in cancer chemoresistance

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Bing Dong ◽  
Shiyu Li ◽  
Shuangli Zhu ◽  
Ming Yi ◽  
Suxia Luo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Complex Process ◽  
Cancer Chemoresistance

AbstractCancer stem cells (CSCs) are a small group of cancer cells, which contribute to tumorigenesis and cancer progression. Cancer cells undergoing epithelial-to-mesenchymal transition (EMT) acquire the chemoresistant ability, which is regarded as an important feature of CSCs. Thus, there emerges an opinion that the generation of CSCs is considered to be driven by EMT. In this complex process, microRNAs (miRNAs) are found to play a key role. In order to overcome the drug resistance, inhibiting EMT as well as CSCs phenotype seem feasible. Thereinto, regulating the EMT- or CSCs-associated miRNAs is a crucial approach. Herein, we conduct this review to elaborate on the complicated interplay between EMT and CSCs in cancer chemoresistance, which is modulated by miRNAs. In addition, we elucidate the therapeutic strategy to overcome drug resistance through targeting EMT and CSCs.

scholarly journals Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Lan Thi Hanh Phi ◽  
Ita Novita Sari ◽  
Ying-Gui Yang ◽  
Sang-Hyun Lee ◽  
Nayoung Jun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Therapeutic Agents ◽  
Therapeutic Approaches ◽  
Tumor Initiating Cells ◽  
Therapeutic Implications ◽  
Key Features

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are suggested to be responsible for drug resistance and cancer relapse due in part to their ability to self-renew themselves and differentiate into heterogeneous lineages of cancer cells. Thus, it is important to understand the characteristics and mechanisms by which CSCs display resistance to therapeutic agents. In this review, we highlight the key features and mechanisms that regulate CSC function in drug resistance as well as recent breakthroughs of therapeutic approaches for targeting CSCs. This promises new insights of CSCs in drug resistance and provides better therapeutic rationales to accompany novel anticancer therapeutics.

Targeting Cancer Stem Cells and Non-Stem Cancer Cells: The Potential of Lipid- Based Nanoparticles

2018 ◽  
Vol 23 (43) ◽  
pp. 6563-6572
Author(s):  
Ana Filipa Cruz ◽  
Nuno Andre Fonseca ◽  
Vera Moura ◽  
Sergio Simoes ◽  
Joao Nuno Moreira
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells
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