scholarly journals Cancer Stem Cells and Targeting Strategies

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 926 ◽  
Author(s):  
Luisa Barbato ◽  
Marco Bocchetti ◽  
Anna Di Biase ◽  
Tarik Regad
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Survival Rates ◽  
Cancer Therapies ◽  
Cellular Processes ◽  
Cancer Initiation ◽  
Enzymatic Inactivation ◽  
Resistance To Chemotherapy ◽  
Made In

Chemoresistance is a major problem in cancer therapy as cancer cells develop mechanisms that counteract the effect of chemotherapeutic compounds, leading to relapse and the development of more aggressive cancers that contribute to poor prognosis and survival rates of treated patients. Cancer stem cells (CSCs) play a key role in this event. Apart from their slow proliferative property, CSCs have developed a range of cellular processes that involve drug efflux, drug enzymatic inactivation and other mechanisms. In addition, the microenvironment where CSCs evolve (CSC niche), effectively contributes to their role in cancer initiation, progression and chemoresistance. In the CSC niche, immune cells, mesenchymal stem cells (MSCs), endothelial cells and cancer associated fibroblasts (CAFs) contribute to the maintenance of CSC malignancy via the secretion of factors that promote cancer progression and resistance to chemotherapy. Due to these factors that hinder successful cancer therapies, CSCs are a subject of intense research that aims at better understanding of CSC behaviour and at developing efficient targeting therapies. In this review, we provide an overview of cancer stem cells, their role in cancer initiation, progression and chemoresistance, and discuss the progress that has been made in the development of CSC targeted therapies.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

scholarly journals Targeting Cancer Stem Cells and Their Niche: Current Therapeutic Implications and Challenges in Pancreatic Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jiangang Zhao ◽  
Jiahui Li ◽  
Hans A. Schlößer ◽  
Felix Popp ◽  
Marie Christine Popp ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Potential Role ◽  
Hematological Malignancies ◽  
Cancer Immunoediting ◽  
Therapeutic Implications ◽  
Novel Treatment ◽  
Cancer Initiation ◽  
Resistance To Chemotherapy

Cancer stem cells (CSCs) have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting. We propose that immunotherapy targeting pancreatic CSCs, in combination with targeting the niche components, may provide a novel treatment strategy to eradicate pancreatic CSCs and hence improve outcomes in pancreatic cancer.

scholarly journals Autophagy and Extracellular Vesicles, Connected to rabGTPase Family, Support Aggressiveness in Cancer Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1330
Author(s):  
Aude Brunel ◽  
Gaëlle Bégaud ◽  
Clément Auger ◽  
Stéphanie Durand ◽  
Serge Battu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Vesicular Trafficking ◽  
Rab Gtpases ◽  
Recycling Process ◽  
Cellular Processes ◽  
Harsh Conditions ◽  
Made In

Even though cancers have been widely studied and real advances in therapeutic care have been made in the last few decades, relapses are still frequently observed, often due to therapeutic resistance. Cancer Stem Cells (CSCs) are, in part, responsible for this resistance. They are able to survive harsh conditions such as hypoxia or nutrient deprivation. Autophagy and Extracellular Vesicles (EVs) secretion are cellular processes that help CSC survival. Autophagy is a recycling process and EVs secretion is essential for cell-to-cell communication. Their roles in stemness maintenance have been well described. A common pathway involved in these processes is vesicular trafficking, and subsequently, regulation by Rab GTPases. In this review, we analyze the role played by Rab GTPases in stemness status, either directly or through their regulation of autophagy and EVs secretion.

scholarly journals Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Tae Hun Kim ◽  
Dong Hoon Suh ◽  
Mi-Kyung Kim ◽  
Yong Sang Song
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Survival Rates ◽  
Genetic Alterations ◽  
Metabolic Reprogramming ◽  
Ovarian Cancer Stem Cells ◽  
Anticancer Efficacy

Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed.

scholarly journals PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2168
Author(s):  
Balawant Kumar ◽  
Rizwan Ahmad ◽  
Swagat Sharma ◽  
Saiprasad Gowrikumar ◽  
Mark Primeaux ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Side Population ◽  
Therapy Resistance ◽  
Fluorescent Reporter ◽  
Combination Treatments ◽  
Gsk 3Β ◽  
Resistance To Chemotherapy

Background: Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Methods: Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. Results: The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Conclusion: Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.

αSMA+ fibroblasts suppress Lgr5+ cancer stem cells and restrain colorectal cancer progression

Oncogene ◽  
2021 ◽  
Author(s):  
Kathleen M. McAndrews ◽  
Karina Vázquez-Arreguín ◽  
Changsoo Kwak ◽  
Hikaru Sugimoto ◽  
Xiaofeng Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Colorectal Cancer Progression

scholarly journals Nanoliposomal Cercodemasoide A and Its Improved Activities Against NTERA-2 Cancer Stem Cells

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098210
Author(s):  
Nguyen Thi Nga ◽  
Do Thi Phuong ◽  
Nguyen Thi Cuc ◽  
Trieu Ha Phuong ◽  
Pham Thi Mai Huong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Drug Carrier ◽  
Free Form ◽  
Cancer Therapies ◽  
3 Dimensional ◽  
Novel Target ◽  
Average Size ◽  
Biopharmaceutical Properties ◽  
First Time

Recently, saponins derived from marine sources have received much attention because of their promising bioactivities, such as anticancer, anti-angiogenesis, and anti-inflammation. In particular, a triterpene saponin from the sea cucumber Cercodemas anceps Selenka, cercodemasoide A (CAN1), showed potent cytotoxicity against various cancer cell lines. Recent evidence has indicated that cancer stem cells (CSCs) could be a novel target for efficient cancer therapies. In order to improve the biopharmaceutical properties of CAN1, the compound was loaded into nanoliposomes as an ideal drug carrier. CAN1 was successfully incorporated into nanoliposomes as small unilamellar liposome vesicles with an average size of 73.39 ± 1.57 nm, zeta potential of −0.299 ± 0.046 mV, polydispersity index of 0.336 ± 0.038, and with an encapsulation efficiency of up to 62.9%. For the first time, CAN1 and its nanoliposomal forms have been shown to have a promising cytotoxic activity against NTERA-2 CSCs, with half-maximal inhibitory concentration (IC50) =1.03 ± 0.04 and 0.41 ± 0.03 µM, respectively. The CAN1 nanoliposomes also presented significantly improved activities in suppressing the growth of NTERA-2 3-dimensional tumorspheres (IC50 = 1.71 ± 0.06 µM) in comparison with the free form ( P < .05). The anti-CSC effects of CAN1 nanoliposomes on NTERA-2 cells were due to their apoptotic induction through enhancing caspase-3 activity (more than 2-fold) and arresting the cell cycle at the S phase ( P < .05). The obtained CAN1-encapsulated nanoliposomes suggest valuable applications in CSC-targeting treatment for more efficient clinical therapy.

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